ISOQUINOLINE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME, AND A PROCESS FOR THE PREPARATION OF THE ACTIVE SUBSTANCE

Abstract: The invention refers to novel isoquinoline derivatives of formula (I), pharmaceutical compositions containing the same, and a process for the preparation of the active ingredient. The novel compounds have an influence on the central nervous system, and possess especially anxiolytic effect.

Description: ISOQUINOLINE DERIVATIVES , PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME , AND A PROCESS FOR THE PREPARATION OF THE ACTIVE SUBSTANCE The invention refers to novel isoquinohne derivatives, pharmaceutical compositions containing the same, and a process for the preparation of the active ingredient The novel compounds have an influence on the central nervous system, and possess especially anxiolytic effect More specifically, the invention refers to a novel isoquinohne derivative of the formula wherein R 1 } R 2 and R 3 represent, independently, a hydrogen atom, a halo atom, a hydroxy group or a Cι -4 alkoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom, a C 1-4 alkoxy group or a tπfluoromethyl group R 7 means a hydrogen atom or a Cι -4 alkyl group, R 8 is a hydrogen atom or a Cι- 4 alkyl group, R5, Re, R9 represent, independently, a hydrogen atom, or R 5 forms with R 6 a valence bond, and simultaneously R 8 forms with R 9 a valence bond, R 10 and Rn represent, independently, a hydrogen atom, a halo atom, a nitro group, a C 1-4 alkoxy group, a trifluoromethyl group or a cyano group, X T and X 2 mean, independently, a hydrogen atom, or X T forms with X 2 a valence bond, furthermore pharmaceutically suitable acid addition salts thereof and a quaternary derivative of the formula wherein Ri, R 2 , R3, R , R5, Re, R7, Re, R9, R10, R11, X1 sπd X 2 are as defined above, R'β stands for a Cι- 4 alkyl group, and A represents a residue of an inorganic or organic acid of the formula HA, or, in formula I, Ri and R 2 are as stated above, R 3 , R 6 and R 7 represent, independently, a hydrogen atom, R 8 forms with R 9 a valence bond, R 4 stands for a hydrogen atom, a Cι -4 alkoxy group or a Cι -6 alkyl group, R 5 means a hidrogen atom or a tπfluoromethyl group, R 10 and Rn represent, independently, a hydrogen atom, a halo atom, a nitro group, a C 1- alkoxy group or a tnfluoro- methyl group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, furthermore pharmaceutically suitable acid addition salts thereof, or, in formula I', Ri and R 2 are as stated above, R 3 , R 5 , Re and R 7 represent, independently, a hydrogen atom, R 8 forms with R 9 a valence bond, R 4 stands for a hydrogen atom or a Cι -6 alkyl group, R 10 and Rn represent, independently, a hydrogen atom, a halo atom, a Cι. 4 alkoxy group or a tπfluoromethyl group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, R's represents a Cι -4 alkyl group, and A represents a residue of an inorganic or organic acid of the formula HA 1-Styrylιsoquιnolιne derivatives having anxiolytic effect are known from the French Patent Applocation of publication No 2 719 586 The aim of the invention is to prepare novel isoquinohne derivatives having more favourable activity than that of the known compounds It was found that the above aim is achieved by the compounds of the formula I and I' having remarkable anxiolytic effect in the so called "light-dark transition" test, while in case of the known 1 -styrylιsoquιnolιne derivatives such an activity is not experienced In addition, the novel compounds do not pr hardly induce the key enzymes of the liver metabolism which take part in the drug metabolism In the description and Claims, in the definition of the substituents, under a halo atom primarily a fluoro, chloro, bromo or lodo atom, preferably a fluoro or chloro atom is meant A Ci -4 alkyl group is a methyl, ethyl, n-propyl, isopropyl, n-butyl, sec -butyl, tert -butyl or isobutyl group, preferably a methyl group A C1-6 alkyl group can represent, for example, also an n-pentyl or an n-hexyl group in addition to the ones listed above under the definition of the Cι- 4 alkyl group A Cι- alkoxy group is primarily a methoxy, ethoxy, n-propoxy or n-butoxy group, preferably a methoxy group A pharmaceutically suitable acid addition salt is an acid addition salt formed with a pharmaceutically suitable inorganic acid such as hydrochloric acid, hydrogen bromide, sulfuπc acid, phosphoric acid etc , or with a pharmaceutically suitable organic acid such as formic acid, acetic acid, fumaπc acid, maleic acid, lactic acid, malic acid, tartaric acid, succinic acid, citric acid, methanesulfonic acid etc n the definition of A, the acid of the formula HA is, preferably, a ann iinnoorrggaanniicc aacciidd ssuucchh aass hhyyddrogen chloride, hydrogen bromide, hydrogen iodide etc A subgroup of the compounds of the invention consists of 1 ,2,3,4-tetrahydroιsoquιnolιne derivatives of the formula wherein Ri, R 2 and R 3 represent, independently, a hydrogen atom, a halo atom, a hydroxy group or a Cι -4 alkoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom or a C 1- alkoxy group, R 7 means a hydrogen atom or a Cι- alkyl group, R 8 is a hydrogen atom or a C 1-4 alkyl group, R 10 and Rn represent, independently, a hydrogen atom, a halo atom, a Ci 4 alkoxy group or a tπfluoromethyl group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, furthermore pharmaceutically suitable acid addition salts thereof and a quaternary derivative of the formula wherein Ri, R 2 , 3, R4, R5, Rε, R7, e, R9, R10, R11, Xi and X 2 are as defined above, R'a stands for a Cι- alkyl group, and A represents a residue of an inorganic or organic acid of the formula HA Preferred 1 ,2,3,4-tetrahydroιsoquιnolιne derivatives of the formula la are those, wherein Ri and R 2 represent, independently, a methoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 3 stands for a hydrogen atom, R 4 means a hydrogen atom, R 7 is a hydrogen atom, R 8 represents a hydrogen atom or a methyl group, R 10 stands for a halo atom, a tnfluoromethyl group or a methoxy group, Rn means a hydrogen atom or a methoxy group, Xi and X 2 mean, independently, a hydrogen atom or Xi forms with X 2 a valence bond, furthermore pharmaceutically suitable acid addition salts thereof and quaternary derivatives of the formula I'a, wherein R-i, R 2 , R3, R 4 , R5, e, R7, R 8 , R9, R10, R11, Xi and X 2 are as defined above, R's stands for a methyl group, and A represents a hahde ion A further subgroup of the compounds of the invention consists of the isoquinohne derivatives of the formula wherein Ri, R 2 and R 3 represent, independently, a hydrogen atom, a halo atom, a hydroxy group or a Cι -4 alkoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom, a C 1- alkoxy group or a tnfluoromethyl group, R 7 means a hydrogen atom or a Cι- alkyl group, R1 0 and Rn represent, independently, a hydrogen atom, a halo atom, a nitro group, a Cι- alkoxy group, a tnfluoromethyl group or a cyano group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, furthermore pharmaceutically suitable acid addition salts thereof and a quaternary derivative of the formula wherein R-i, R 2 , R 3 , R 4 , R 7 , R10, Rn, Xi and X 2 are as defined above, R' 8 stands for a Cι- alkyl group, and A represents a residue of an inorganic or organic acid of the formula HA Preferred isoquinohne derivatives of the formula lb are those, wherein Ri, R 2 and R 3 represent, independently, a hydrogen atom or a methoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom, a Cι_ 4 alkoxy group or a tnfluoromethyl group, R 7 means a hydrogen atom or a methyl group, R 10 represent a hydrogen atom, a halo atom, a nitro group, a methoxy group, a tnfluoromethyl group or a cyano group, Rn is a hydrogen atom or a methoxy group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, furthermore pharmaceutically suitable acid addition salts thereof and a quaternary derivative of the formula I'b, wherein Ri, 2, R3, R , R7, R10, R11, Xi and X 2 are as defined above, R'a stands for a methyl group, and A represents a ha de ion Another subgroup of the compounds of the invention consists of the 3,4-dιhydroιsoquιnohne derivatives of the formula wherein Ri and R 2 represent, independently, a hydrogen atom, a halo atom, a hydroxy group or a C1-4 alkoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom, a Cι- alkoxy group or a Cι -6 alkyl group R 5 means a hydrogen atom or a tπfluoromethyl group, R1 0 and Rn represent, independently, a hydrogen atom, a halo atom, a nitro group, a Cι- alkoxy group or a tπfluoro- methyl group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, furthermore pharmaceutically suitable acid addition salts thereof Preferred 3,4-dιhydroιsoquιnohne derivatives of the formula XIV are those, wherein Ri and R 2 represent, independently, a hydrogen atom, a chloro atom, a hydroxy group or a methoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom or a Cι- 6 alkyl group, R 5 means a hydrogen atom, R 10 and R represent, independently, a hydrogen ator , a fluoro atom, a methoxy group or a tnfluoromethyl group, Xi and X 2 mean, independently, a hydrogen atom, or X T forms with X 2 a valence bond, furthermore pharmaceutically suitable acid addition salts thereof Especially preferred 3,4-dιhydroιsoquιnohπe derivatives of the formula XIV are those, wherein Ri forms with R 2 a methylenedioxy group, R 4 stands for a Cι. 6 alkyl group, R 5 means a hydrogen atom or a tnfluoromethyl group, R 10 and Rn represent, independently, a hydrogen atom, a methoxy group or a tnfluoromethyl group, Xi forms with X 2 a valence bond, furthermore pharmaceutically suitable acid addition salts thereof A still further subgroup of the compounds of the invention consists of the 3,4-dιhydroιsoquιπolιnιum derivatives of the formula wherein Ri and R 2 represent, independently, a hydrogen atom, a halo atom, a hydroxy group or a Cι -4 alkoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom or a d- 6 alkyl group R's means a Cι- alkyl group, R-io and Rn represent, independently, a hydrogen atom, a halo atom, a Ci alkoxy group or a tnfluoromethyl group, Xi and X 2 mean, independently, a hydrogen atom, or X T forms with X 2 a valence bond, A represents a residue of an inorganic or organic acid of the formula HA Preferred 3,4-dιhydroιsoquιnohnιum derivatives of the formula XI are those, wherein Ri and R 2 represent, independently, a hydroxy group, a chloro atom or a methoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom or a Cι -3 alkyl group, R's means a methyl group, R 10 and Rn represent, independently, a hydrogen atom, a halo atom or a tnfluoromethyl group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, A represents a residue of an inorganic acid of the formula HA Especially preferred 3,4-dιhydroιsoquιnolιnιum derivatives of the formula XI are those, wherein Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom or a Cι. 3 alkyl group, R's means a methyl group, R 10 and Rn represent, independently, a hydrogen atom, a fluoro atom or a tnfluoromethyl group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, A represents a bromide ion or a iodide ion The compounds of the invention are prepared as follows: a) for the preparation of an isoquinohne derivative of the formula lb, wherein R 1 t R 2 , R 3 , R 4 , R 7 , Rι 0 and Rn are as defined in connection with formula I, Xi forms with X 2 a valence bond, condensing a 1 -methylisoquinoline of the formula wherein Ri, R 2 , R 3 , R 4 and R 7 are as stated above, with an aldehyde of the formula wherein Rι 0 and Rn are as defined in connection with formula I; or b) for the preparation of an isoquinohne derivative of the formula lb, wherein R 1 ( R 2 , R 3 , R , R 7 , Rio, Rn, Xi and X 2 are as defined in connection with formula I, subjecting a 3,4- dihydroisoquinoline derivative of the formula wherein Ri, R 2 , R 3 , R , R 7 , R10, Rn, Xi and X 2 are as stated above, Rι 3 stands for a hydrogen atom, to catalytical dehydrogenation; or c) for the preparation of a 1 ,2,3,4-tetrahydroisoquinoline derivative of the formula la, wherein Ri, R 2 , R 3 , R 4 , R 7 , ,Rιo, Rn, Xi and X 2 are as defined in connection with formula I, R 8 represents a hydrogen atom, hydrogenizing a 3,4- dihydroisoquinoline derivative of the formula IV, wherein Ri, R 2 , R3, R 4 , R7, R10, R11, Xi and X 2 are as stated above, R 13 stands for a hydrogen atom; or d) for the preparation of a 1 ,2,3,4-tetrahydroisoquinoline derivative of the formula la, wherein Ri, R 2 , R 3 , R 4 , R 7 , R10, Rn, . X-, and X 2 are as defined in connection with formula I, R 8 represents a Cι_ 4 alkyl group, reacting a 3,4-dihydro- isoquinolinium derivative of the formula wherein Ri, R 2 , R 3 , R 4 , R7, R10 Rn, Xi and X 2 are as stated above, Rι 2 stands for a C 1 4 alkyl group, A is as defined in connection with formula I', with a reducing agent, or e) for the preparation of an isoquinohne derivative of the formula lb, wherein Ri, R 2 , R 3 , R7, R10 Rn, Xi and X 2 a e as defined in connection with formula I, R 4 stands for a tnfluoromethyl group, reacting a 3,4-dιhydroιsoquιnohne derivative of the formula IV, wherein R 1 ( R 2 , R 3 , R 4 , R 7 , R10 Rn, Xi and X 2 are as stated above, R 13 represents a Cι -4 alkoxy group, with an alkali metal hydroxide, or f) for the preparation of an isoquinohne derivative of the formula lb, wherein Ri, R 2 , R 3 , R7, Rio and Rn are as defined in connection with formula I, R 4 stands for a tnfluoromethyl group, Xi forms with X 2 a valence bond, reacting a 1 -methyl-3,4- dihydroisoquinohne of the formula wherein R 1 ( R 2 , R 3 , R and R 7 are as stated above, Rι 3 stands for a Cι -4 alkyl group, with an aldehyde of the formula III, wherein R 10 and Rn are as stated above, in the presence of a condensing agent, or g) for the preparation of a 3,4-dιhydroιsoquιπolιne derivative of the formula XIV, wherein Ri, R 2 , R 4 , R 5 , R10, Rn, Xi and X 2 are as defined in connection with formula I, cychzing an acid amide of the formula wherein Ri, R 2 , R 4 , R1 0 , Rn, Xi and X 2 are as stated above, R 3 stands for a hydrogen atom, and R 3 represents a hydrogen atom or a tnfluoromethyl group, or h) for the preparation of a 3,4-dιhydroιsoquιnohnιum derivative of the formula XI, wherein Ri, R 2 , R 4 , R' 8 , R10, Rn, Xi and X 2 are as defined in connection with formula I, A represents a residue of an inorganic acid of the formula HA, reacting a 3,4- dihydroisoquinohne derivative of the formula wherein Ri, R 2 , R 4 , Rio, Rn, Xi and X 2 are as defined above, with a reagent of the formula R' 8 -A, wherein R' 8 and A are as stated above, or / i) for the preparation of a 3,4-dιhydroιsoquιnohnιum derivative of the formula XI, wherein Ri, R 2 , R 4 , R's, Rio, Rn, Xi and X 2 are as defined in connection with formula I, A represents a residue of an inorganic acid of the formula HA, reacting a 1 ,2,3,4- tetrahydroisoquinohnium derivative of the formula wherein Ri, R 2 , R 4 , R' 8 , R 10 , Rn, Xi and X 2 are as stated above, with an oxidizing agent, and, if desired, converting an obtained compound of the formula I, wherein Ri, R 2 , R3, R 4 , R5, Re, R7, Ra, R9, R10 and R , are as defined in connection with formula I, Xi forms with X 2 a valence bond, to a corresponding compound of the formula I, wherein Xi and X 2 represent a hydrogen atom, by catalytical hydrogenation, or converting an obtained 1 ,2,3,4-tetrahydroιsoquιnohne derivative of the formula la, wherein R 1 ? R 2 , R 3 , R 4 , R 7 , R10, Rn, X T and X 2 are as defined in connection with formula I, R 8 stands for a hydrogen atom, to a compound of the formula la, wherein R 8 represents a C 1- alkyl group, by reaction with a Cι- alkyl hahde, or converting an obtained compound of the formula I to a pharmaceutically suitable acid addition salt or liberating the base from the salt, or converting an obtained compound of the formula I to a quaternary derivative of the formula I', wherein R 1 ( R 2 , R 3 , R 4 , R5, Re, R7, Re, R9, R10, R11, Xi and X 2 are as defined in connection with formula I, R' 8 represents a Cι -4 alkyl group, A stands for a residue of an inorganic or organic acid of the formula HA, by reaction with a compound of the formula R' 8 -A, wherein R' 8 and A are as stated above, or converting an obtained quaternary isoquinohne derivative of the formula I'b, wherein R-,, R 2 , R 3 , R 4 , R 7 , Rι 0 , Rn, Xi and X 2 are as defined in connection with formula I, R' 8 stands for a Cι- alkyl group, A represents a residue of an inorganic or organic acid of the formula HA, to a compound of the formula la, wherein Ri, R 2 , R 3 , R 4 , R 7 , Rι 0 , Rn, Xi and X 2 are as stated above, R 8 stands for a Cι. alkyl group, by reaction with a reducing agent In process a) of the invention, 1 -methyhsoquιnohne of the formula II is condensed with the aldehyde of the formula I II using the process known from French Patent Application published under No 2 719 586 In process b) of the invention, the 3,4-dιhydroιsoquιnohne derivative of the formula IV is dehydrogenized in an analogous manner known from the literature [Heterocyclic Compounds, 38, 386-387, Ed John Wiley and Sons, Inc , New York, (1994)] In process c) of the invention, the 3,4-dιhydroιsoquιnolιne derivative is hydrogenized using known literature processes [Houben-Weyl Meth Org Chem , 4/1 c, 121 , 271 -281 , 365, 401 , Georg Thieme Verlag, Stuttgart, (1981 )] In process d) of the invention, the reduction of the 3,4- dihydroisoquinohnium derivative of the formula V is carried out using methods described in the literature cited in connection with process c) In process e) of the invention, the alkoxy group in position 4 is eliminated with an alkali metal hydroxide, preferably potassium hydroxide Process f) of the invention can be performed in a similar way as process a) As condensing agent preferably a carboxylic anhydride, suitably acetic anhydride is used In process g) of the invention, the acid amide of the formula VIII is cyc zed in a manner known from the literature [Heterocyclic compounds, Ed J Wiley and Sons, Inc , 38/3. 85-89 (1994), 38/1 , 173-175 (1994)] In process h) of the invention, preferably a Cι -4 alkyl hahde, suitably methyl iodide or methyl bromide is used as the reagent of the formula R' 8 -A, and the reaction is carried out in the presence of an indifferent organic solvent at 10 to 160 °C, in general The organic solvent can be apolar such as benzene, toluene, xylene, dichloromethane, etc , or polar protic such as methanol, ethanol etc Process i) of the invention is performed in an analogous manner as the processes known from the literature [Houben- Weyl, Meth Org Chem , Georg Thieme Verlag, Stuttgart, 4/1 c. 517-518 (1981)] An obtained isoquinohne derivative can be converted to another compound of the formula I in a manner known perse For example, a styryl derivative, wherein X forms with X 2 a valence bond, can be transformed into a compound of the formula I, wherein Xi and X 2 stand for a hydrogen atom by catalytical hydrogenation [Houben-Weyl Meth Org Chem , 4/1 d, 580-581 , Georg Thieme Verlag, Stuttgart, (1981 )] The nitrogen atom of a 1 ,2,3,4-tetrahydroιsoquιnohne derivative of the formula la, wherein R 8 represents a hydrogen atom, can be alkylated in a manner known per se, for example using an alkyl hahde The compound of the formula I can be reacted with a compound of the formula R' 8 -A, preferably a C 1 - 4 alkyl ha de to obtain a quaternary compound of the formula I' The reaction is carried out in an apolar solvent such as benzene, toluene, xylene, dichloromethane, dichloroethane, etc , or a polar protic solvent such as an alkanol at a temperature from 10 to 160 °C A quaternary isoquinohne derivative of the formula I'b can be reduced to obtain the corresponding 1 ,2,3,4-tetrahydroιso- quinohne of the formula la The reduction is performed using the methods described in the literature cited in connection with process c) The 1 -methyhsoquιnohne derivatives of the formula II are partly known compounds The compounds of the formula II, wherein R 4 stands for a tnfluoromethyl group, can be prepared by the reaction of a 1 -methyl-1 ,2-dιhydroιsoquιnohne and potassium hydroxide The 1 -methyl-1 ,2-dιhydroιsoquιnohne of the formula VI is prepared by cychzing an acid amide of the formula wherein Ri, R 2 and R 3 are as defined in connection with formula I, R 4 stands for a tnfluoromethyl group, Rι 3 represents a C 1 - 4 alkoxy group The cychzation reaction is carried out in a manner known from the literature [Heterocyclic Compounds, Ed J Wiley and Sons, Inc , 38/3, 65-89 (1994), 38/1 , 173-175 (1994)] The aldehydes of the formula III are known compounds that are commercially available The 1 ,2-dιhydroιsoquιnohne derivatives of the formula IV are novel compounds that are prepared by cychzing an acid amide of the formula VIII, wherein Ri, R 2 , R 3 , R 4 , R 10 , Rn, Xi and X 2 are as defined in connection with formula I, R 3 represents a Ci -4 alkoxy group The cychzation reaction is performed an an analogous manner as the cychzation of the acid amide of the formula VII The acid amide of the formula VIII can be prepared by reacting an acid derivative of the formula wherein R 10 , Rn, Xi and X 2 are as defined in connection with formula I, with a phenylethylamine of the formula wherein Ri, R 2 , R 3 and R 4 are as defined in connection with formula I, R 13 stands for a C 1 - 4 alkoxy group, in an analogous manner as described in the literature [Houben-Weyl Meth Org Chem , E5/2, 993-1 100, Georg Thieme Verlag, Stuttgart, (1981 )] The acid derivatives of the formula IX and the phenylethylamines of the formula X are commercially available The tnfluoromethyl derivatives of the formula X can be prepared from the corresponding cyanohydπne of the formula wherein Ri, R 2 , R and R 5 are as defined above, by reduction The cyanohydnne of the formula XV can be obtained by reacting the corresponding acetophenone of the formula / wherein Ri and R 2 are as defined above, with an alkali metal cyanide The 1 ,2-dιhydroιsoquιnolιnιum derivative of the formula V can be prepared from the corresponding 1 ,2-dιhydroιsoquιnolιne by reaction with an alkylating agent of the formula R1 2 -A, wherein Rι 2 represents a C, 4 alkyl group, A is a residue of an inorganic or organic acid of the formula HA The 3,4-dιhydroιsoquιnolιne derivative of the formula XII is prepared by cychzing an acid amide of the formula VIII The cychzation reaction is carried out in a manner described under the cychzation of the acid amide of the formula VII The pharmacological effect of the compounds of the invention have been proved by the following experiments 1. Light-dark transitions 18-38 g male NMRI mice were used for the experiments The animals were kept in reverse light-dark cycle for two weeks before the experiment in polycarbonate cages Behavioral testing was conducted in two-compartment (lit and dark) automated test chambers, horizontal and vertical activities were recorded as interruptions of infrared beams Test compounds were suspended in 0 4 % methylcellulose solution and were administered intrapentoneally 30 mm before testing Under the test conditions, the animals tend to explore the new environment, however, they are anxious of aversive stimuli (light) in the lit area Therefore, exploration of the new environment is limited Anxiolytic compounds reduce the time spent with exploration in the dark area and/or increase the exploration activity in the lit compartment The compound tested has been considered effective when the time spent with exploration has been statistically significantly changed compared to untreated controls in either one or both compartments Minimal effective doses (i e the lowest dose producing statistically significant effects) were determined for each compounds investigated [Costall, B et al , Pharm Biochem Behav , 32, 777-785 (1989), Young, R and Johnson, D N , Pharm Biochem Behav , 40, 739-743 (1991 )] 1 -(4-Tπfluoromethylstyryl)-6,7-methylenedιoxyιsoquιnohne described in French Patent Application published under No 2 719 586 has been used as the reference compound The results obtained are summarized in Table I Table I Compound (Example No.) Minimum effective dose (mg/kg ip.) 21 10 47 10 51 30 / 53 10 55 3 82 10 83 30 84 1 1 -(4-tπfluoromethylstyryl)- -6,7- above 30 methylenedioxyisoquinoline Data in Table I clearly show that the examined compounds of the invention display significant effect in the "light-dark transition" test, while the known reference compound is ineffective 2. Measurement of spontaneous motor activity Every group consisted of 30 animals (15 males, 15 females) weighing 20 to 25 g The animals were treated with the test compound or the vehicle (control group) The compounds to be tested were suspended in 0 4 % methylcellulose solution and were administered per os in 20 ml/kg treatment volume to the animals 60 minutes before test session The method provides general information on the influence of the investigated compound on the natural locomotor activity of experimental animals, particularly on sedative effects For anxiolytic compounds, the presence or absence of sedative potential is crucial for further development (the latter is desirable) Measurement was conducted in a 10 channel "Digital moti ty meter" Locomotor activity of three mice per channel was determined by recording the number of interruptions of three infrared beams for 30 minutes ID 50 (50 % inhibition dose) values were calculated for each investigated compounds [Borsy, I et al , Arch Int Pharmacodyn , 124, 180-190 (1960), Stille, G et al , II Farmaco Ed Pr , 26, 603-625 (1971 )] The results obtained are summarized in Table II Diazepam [i e 7-chloro-1 ,3-dιhydro-1 -methyl-5-phenyl-2H-1 ,4-benzo- dιazepιne-2-one] was used as reference compound Table II Compound (Example No.) IDso (mg/kg p.o.) 10 higher than 100 21 higher than 100 45 higher than 100 47 higher than 100 53 higher than 100 55 higher than 100 82 higher than 100 83 higher than 100 84 higher than 100 diazepam 18 4 Data in Table II clearly show that the compounds of the invention did not influence the spontaneous motor activity of the animals even in a dose more than five times higher than that of the ID 50 value of diazepam 3. Measurement of enzyme induction Wistar rats weighing 140 to 160 g were used for the experiments The compounds to be tested were suspended in 0 4 % methylcellulose solution and administered in 100 mg/kg daily per os dose for 3 consecutive days β-Naphthoflavone treatment was used as positive control in 25 mg/kg per os dose. The typical reaction for CYP1 A isoenzyme has been monitored by the measurement of ethoxyresoruphine deethylase (EROD) activity according to the method of Pohl, R.J. and Fouts, J.R., Anal. Biochem., 107, 150-155 (1980). Control values from untreated animals have been considered as 100 %, and EROD activities have been expressed as percent of untreated control. The results obtained are summarized in Table III 1 -(4-Trifluoromethylstyryl)-6,7- methylenedioxyisoquinohne has been used as the reference compound. Table III Compound (Example No.) Relative EROD activity (percentage of control) 10 99 21 87 45 103 47 102 51 133 53 74 55 1 1 1 82 1 14 83 97 84 75 1 -(4-tπfluoromethylstyryl)-6,7- 570 methylenedioxyisoquinohne β-naphthoflavone 550 Data in Table III clearly show that treatment with the reference isoquinohne derivative resulted in more than five times elevation in enzyme activity (similarly to the β-naphthoflavone used as positive control) while results obtained with the compounds of the invention are about the values of untreated control According to the above summarized experimental results, the compounds of the invention display marked CNS, especially anxiolytic effects The anxiolytic activity is significant in the "light-dark transition" test, while the known 1 -styryhsoquinohne derivatives were found to be practically ineffective in this test Moreover, the novel compounds did not influence spontaneous motor activity in a dose more than five times higher than that of the ID 50 value of the reference compound diazepam Unlike the known anxiolytic 1 -styrylιsoquιnohne derivatives, the compounds of the invention did not influence the key enzymes of hepatic drug metabolism The low and insignificant enzyme induction potency of the novel compounds is of great importance from drug safety approaches Thus, the novel isoquinohne derivatives of the formula I can be / used as active ingredients in pharmaceutical compositions The pharmaceutical compositions of the invention contain a therapeutically active amount of the compound of the formula I or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I' and one or more conventional carπer(s) The pharmaceutical compositions of the invention are suitable for peroral, parenteral or rectal administration or for local treatment, and can be solid or liquid The solid pharmaceutical compositions suitable for peroral administration may be powders, capsules, tablets, film-coated tablets, microcapsules etc , and can comprise binding agents such as gelatine, sorbitol, poly(vιnylpyrrolιdone) etc , filling agents such as lactose, glucose, starch, calcium phosphate etc , auxiliary substances for tabletting such as magnesium stearate, talc, poly(ethylene glycol), silica etc , wetting agents such as sodium laurylsulfate etc as the carrier The liquid pharmaceutical compositions suitable for peroral administration may be solutions, suspensions or emulsions and can comprise e g suspending agents such as gelatine, carboxymethylcellulose etc , emulsifiers such as sorbitane monooleate etc , solvents such as water, oils, glycerol, propylene glycol, ethanol etc , preservatives such as methyl p- hydroxybenzoate etc as the carrier Pharmaceutical compositions suitable for parenteral administration consist of sterile solutions of the active ingredient, in general Dosage forms listed above as well as other dosage forms are known per se, see e g Remington's Pharmaceutical Sciences, 18th Edition, Mack Publishing Co , Easton, USA (1990) The pharmaceutical compositions of the invention contain, in general, 0 1 to 95 0 per cent by mass of a compound of the formula I or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I' A typical dose for adult patients amounts to 0 1 to 1000 mg of the compound of the formula I, daily The above dose can be administered in one or more portions The actual dosage depends on many factors and is determined by the doctor The pharmaceutical compositions of the invention are prepared by admixing a compound of the formula I or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I' to one or more carrιer(s), and converting the mixture obtained to a pharmaceutical composition in a manner known per se Useful methods are known from the literature, e g Remington's Pharmaceutical Sciences mentioned above One subgroup of the pharmaceutical compositions of the invention contains a 1 ,2,3,4-tetrahydroιsoquιnohne of the formula la or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I'a A further subgroup of the pharmaceutical compositions of the invention contains an isoquinohne derivative of the formula lb or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I'b Another subgroup of the pharmaceutical compositions of the invention contains a 3,4-dιhydroιsoquιnolιne derivative of the formula XIV or a pharmaceutically suitable acid addition salt thereof A still further subgroup of the pharmaceutical compositions of the invention contains a 3,4-dιhydroιsoquιnohnιum derivative of the formula XI The invention includes also a method of treatment in which a patient suffering from especially a disease of the central nervous system is treated with a non-toxic dose of a 3,4- dihydroisoquino ne derivative of the formula I or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I' In addition, the invention includes the use of an isoquinohne derivative of the formula I or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I' for the preparation of a pharmaceutical composition having anxiolytic effect The invention is further elucidated by means of the following Examples Preparation of the acid amides of the formula VII 1 ) N-Acetyl-3 3,3-trιfluoro-2-methoxy-2-(3-methoxyphenyl)- propylamine To a solution of 12 46 g (50 mmoles) of 3,3,3-trιfluoro-2- methoxy-2-(3-methoxyphenyl)propylamιne in 90 cm 3 of ethyl acetate, 4 91 cm 3 (5 31 g, 52 mmoles) of acetic anhydride are added, drop by drop, at 0 °C. The reaction mixture is stirred at room temperature for 2 hours, then poured onto 90 cm 3 of water. The two phases are separated. The aqueous phase is extracted twice using 60 cm 3 of ethyl acetate each time. The combined organic phases are dried over anhydrous magnesium sulfate, and the solvent is evaporated. Thus, 14.50 g (98 %) of the colourless title compound are obtained. M.p.: 74-75 °C (2-propanol-water). Analysis: for Cι 3 Hι 6 F 3 N0 3 (291.27) calculated: C 53.61 %, H 5.54 %, N 4.81 %; found: C 53.48 %, H 5.50 %, N 4.75 %. IR (Kbr, cm "1 ): 3330, 1613, 1119. 1 H-NMR (CDCI 3 250 MHz) δ: 7.34 (1 H, t, J=8.3 Hz), 7.03 (2H, m), 6.93 (1 H, s), 5.79 (1 H, s), 4.13 (1 H, dd, H=14.8 Hz, J=5.4 Hz), 3.90 (1 H, ddd, J=I4.8 Hz, J=5.4 Hz, J=1.4 Hz), 3.83 (3H, s), 3,35 (3H, q, J=0.9 Hz), 1.99 (3H, s). 13 C-NMR (CDCI 3 62.9 MHz) δ: 170.1 , 159.9, 135.0, 129.8, 124.9 (q, 1 Jc F =288.8 Hz), 119.6, 114.5, 113.9, 80.7 (q, 2 J CF =26.3 Hz), 55.4, 52.7, 41.0, 23.2. 2) N-Acetyl-3,3,3-trifluoro-2-methoxy-2-(3,4-methylenedioxy- phenyOpropylamine The procedure described in the preparation of the starting compound 1) is followed to obtain the title compound. Yield: 98 %. M.p.: 119-120 °C (2-propanol-water). Analysis: for C 13 Hι 4 F 3 N0 4 (305.25) calculated C 51 15 %, H 4 62 %, N 4 59 %, found C 51 38 %, H 4 67 %, N 4 69 % IR (KBR cm "1 ) 3340, 1679, 1171 , 1111 1 H-NMR (CDCI 3 200 MHz) δ 6 97 (1 H, s), 6 93 (1 H, d, J=8 2 Hz), 6 83 (1 H, d, J=8 2 Hz), 6 00 (1 H, d, J=1 4 Hz), 5 99 (1 H, d, J=1 4 Hz), 5 86 (1 H, bs), 4 09 (1 H, dd, J=14 8 Hz, J=5 3 Hz), 3 89 (1 H, ddq, J=14 8 Hz, J=5 3 Hz, J=1 2 Hz), 3 33 (3H, s), 1 99 (3H, s) 13 C-NMR (CDCI 3 , 100 6 MHz) δ 170 0, 148 2, 126 8, 124 7 (q, 1 J CF =288 0 Hz), 121 1 , 108 2, 107 8, 101 4, 80 3 (q, 2 J CF =26 6 Hz), 52 2, 40 7, 23 1 Preparation of 1-methyl-3,4-dihydroisoquinolines of the formula VI 3) 1 -Methyl-4,6-dιmethoxy-4-tπfluoromethyl-3,4-dιhydro- isoquinohne 2 91 g (10 mmoles) of N-acetyl-3,3,3-trιfluoro-2-methoxy-2-(3- methoxyphenyl)propylamιne are stirred in 4 46 cm 3 (7 67 g, 50 mmoles) of phosphor(V) trichloride oxide at 85 °C for 16 hours The reaction mixture cooled to room temperature is poured onto 40 cm 3 of ice water The pH is adjusted to 11 with concentrated aqueous ammonia, and the solution is extracted three times using 30 cm 3 of ethyl acetate each time The combined organic phases are dried over anhydrous magnesium sulfate, and evaporated The crude base is recrystalhzed from acetonitnle Thus, 2 22 g (81 %) of the colourless title compound are obtained M p 203-204 °C (acetonitnle) Analysis for Cι 3 Hι 4 F 3 N0 2 (273 25) calculated C 57 14 %, H 5 16 %, N 5 13 %, found C 57 27 %, H 5 26 %, N 5 11 % IR(Kbr, cm 1 ) 1609, 1247, 1178 1 H-NMR (CDCI 3 250 MHz) δ 7 56 (1 H, d, J=8 7 Hz), 7 19 (1 H, dd, J=2 6 Hz, J=0 8 Hz), 7 00 (1 H, dd, J=8 7 Hz, J=2 6 Hz), 4 12 (1 H, dq, J=17 5 Hz, J=1 5 Hz), 4 02 (1 H, dq, J=17 5 Hz, J=1 5 Hz), 3 88 (3H, s), 3 27 (3H, s), 2 39 (3H, t, J=1 7 Hz) 13 C-NMR (CDCI 3 62 9 MHz) δ 162 7, 161 5, 131 2, 127 8, 125 1 (q, 1 J CF =287 2 Hz), 123 2, 114 7, 112 4, 74 9 (q, J CF =27 9 Hz), 55 3, 52 1 , 48 9, 23 0 4) 1 -Methyl-6,7-methylenedιoxy-4-methoxy-4-trιfluoromethyl- 3,4-dιhydroιsoquιnohne The procedure described in the preparation of starting compound 3) is followed to obtain the title compound recrystalhzed from acetonitnle Yield 75 % M p 203-204 °C (acetonitnle) Analysis for C 13 Hι 2 F 3 N0 3 (287 23) calculated C 54 36 %, H 4 21 %, N 4 88 %, found C 54 19 %, H 4 27 %, N 4 79 % IR (KBr, cm 1 ) 1606, 1286, 1173 1H-NMR (CDCI 3 400 MHz) δ 7 13 (1 H, q, J=0 9 Hz), 7 07 (1 H, s), 6 06 (1 H, d, J=0 9 Hz), 6 06 (1 H, d, J=1 3 Hz), 4 01 (1 H, ddd, J=16 8 Hz, J=3 0 Hz, J=1 5 Hz), 4 00 (1 H, dd, J=16 8 Hz, J=1 5 Hz), 3 24 (3H, s), 2 37 (3H, t, J=1 7 Hz) 1 3 C-NMR (CDCI 3 100 6 MHz) δ 162 4, 149 8, 148 9, 125 2 (q, 1 J CF =287 3 Hz), 125 1 , 107 3 (q, 3 J CF =1 9 Hz), 106 4, 102 0, 75 2 (q, 2 J CF = 27 6 Hz), 52 1 , 49 1 , 23 6 Preparation of 1-methylisoquinolines of the formula II: 5) 1 -Methyl-6-methoxy-4-trιfluoromethyhsoquιnohne To a solution of 2 73 g (10 mmoles) of 1 -methyl-4,6-dιmethoxy- 4-trιfluoromethyl-3,4-dιhydroιsoquιnohne in 20 cm 3 of 2- propanol, 0 84 g (15 mmoles) of powdered potassium hydroxide are added The reaction mixture is stirred at 50 °C for 2- hours, then evaporated The residue is rubbed with 10 cm 3 of water, and filtered The crystals are washed with 5 cm 3 of water The crude product is recrystalhzed from petroleum ether (b.p 80- 100 °C) Thus, 2 05 g (85 %) of the colourless title compound are obtained M p 95-96 °C (petroleum ether) Analysis for Cι 2 Hι 0 F 3 NO (241 21 ) calculated C 59 75 %, H 4 18 %, N 5 81 %, found C 59 57 %, H 4 13 %, N 5 76 % IR (Kbr crrϊ 1 ) 1624, 1256, 1165, 1126 1 H-NMR (CDCI 3 250 MHz) δ 8 64 (1 H, d, 0 7 Hz), 8 10 (11-1, d, J=9 0 Hz), 7 35-7 20 (2H, m), 3 98 (3H, s), 2 96 (3H, s) 13 C-NMR (CDCI 3 62 9 MHz) δ 162 7, 161 5, 140 8 (q, 3 J CF =6 7 Hz), 133 7, 128 0, 124 7 (q, 1 J CF =272 4 Hz), 122 6, 120 2, 1 18 0 (q, 2 J CF =28 9 Hz), 102 1 , 55 4, 22 8 6) 1 -Methyl-6,7-methylenedιoxy-4-trιfluoromethyhsoquιnohne The procedure described in the preparation of the starting compound 5) is followed to obtain the title compound as colourless solids Yield 90 % M p 139-141 °C (petroleum ether, b p 80-100 °C) Analysis for d 2 H 8 F 3 N0 2 (255 196) calculated C 56 48 %, H 3 16 %, N 5 49 %, found C 56 33 %, H 3 14 %, N 5 45 % IR (Kbr, cm "1 ) 1477, 1 167, 1 1 12 1 H-NMR (CDCI 3 200 MHz) δ 8 58 (1 H, s), 7 44 (1 H, s), 7 40 (1 H, q, J=1 8 Hz), 6 17 (2H, s), 2 91 (3H, s) 13 C-NMR (CDCI 3 100 6 MHz) δ 161 1 , 151 8, 148 6, 139 3 (q, 3 J CF =6 5 HZ), 130 1 , 124 7 (q, 1 J CF =273 1 Hz), 124 6, 1 18 6 (q, 2 J CF =30 5 HZ), 102 2, 100 6, 23 3 Preparation of acid amides of the formula VIII: 7) N-Cιnnamoyl-3,3,3-trιfluoro-2-methoxy-2-(3-methoxy- phenyl)propylamιne To a suspension of 12 46 g (50 mmoles) of 3,3,3-trιfluoro-2- methoxy-2-(3-methoxyphenyl)propιonιtrιle, 30 cm 3 of diethyl ether, 5 30 g (50 mmoles) of sodium carbonate and 50 cm 3 of water, a solution of 8 33 g (50 mmoles) of cinnamoyl chloride in 50 ml of diethyl ether are added at 0 °C, drop by drop, and the reaction mixture is stirred for 2 hours The precipitated crystals are filtered, washed with 20 cm 3 of diethyl ether Thus, 16 39 g (90 %) of the title compound are obtained M p 72-73 °C (2-propanol, water) Analysis for C 2 oH 20 F 3 N0 3 (379 38) calculated C 63 32 %, H 5 31 %, N 3 69 %, found C 63 12 %, H 5 27 %, N 3 76 % IR (Kbr, cm "1 ) 1662, 1630, 1179 1 H-NMR (CDCI 3 250 MHz) δ 7 63 (1 H, d, J=15 6 Hz), 7 55-7 45 (2H, ), 7 40-7 30 (4H, m), 7 10-7 05 (2H, m), 6 99-6 90 (1 H, m), 6 39 (1 H, d, J=15 6 Hz), 5 89 (1 H, bs), 4 27 (1 H, dd, J=15 0 Hz, J=5 4 Hz), 4 08 (1 H, dd, J=15 0 Hz, J=5 4 Hz), 3 83 (3H, s), 3 39 (3H, q, J=0 8 Hz) 13 C-NMR (CDCI 3 50 3 MHz) δ 165 7, 159 8, 141 7, 135 . 0, 134 6, 129 8, 129 7, 128 8, 127 8, 124 9 (q, 1 J CF =288 4 Hz), 120 1 , 1 19 5, 1 14 5, 1 13 6, 80 6 (q, 2 J C =26 3 Hz), 55 3, 52 6, 40 9 8) N-(4-Fluorocιnnamoyl)-3,3,3-trιfluoro-2-methoxy-2-(3- methoxyphenyl)propylamιne The procedure described in the preparation of the starting compound 7) is followed to obtain the title compound as colourless solids Yield 75 % M p 100-101 °C (2-propanol, water) Analysis for C 20 Hι 9 F 4 NO 3 (397 37) calculated C 60 45 %, H 4 82 %, N 3 52 %, found C 60 31 %, H 4 80 %, N 3 55 % IR (Kbr, cm "1 ) 3293, 1661, 1628, 1227, 1149 1 H-NMR (CDCI 3 250 MHz) δ 7 59 (1 H, d, J=15 6 Hz), 7 51-7 44 (2H, m), 7 40-7 30 (1 H, m), 7 10-7 00 (4H, m), 7 00-6 91 (1 H, m), 6 31 (1 H, d, J=15 6 Hz), 5 88 (11-1, bs), 4 27 (11-1, dd, J=14 9 Hz, J=5 4 Hz), 4 06 (1 H, ddd, J=14 9 Hz, J=5 4 Hz, J=1 3 Hz), 3 83 (3H, s), 3 39 (3H, s) 13 C-NMR (CDCI 3 62 9 MHz) δ 163 5 (d, 1 J CF =249 2 Hz), 159 7, 140 4, 134 8, 130 7, 119 6 (d, 2 J CF =8 8 Hz), 129 3 (q, 1 J CF =289 1 Hz), 122 4, 119 6, 119 4, 117 8, 115 8 (d, 2 J CF =22,6 Hz), 1 14 3, 1 13 5, 80 5 (q, 2 J CF = 27 2 Hz), 55 2, 52 5, 40 9 9) N-(4-Trιfluoromethylcιnnamoyl)-3,3,3-trιfluoro-2-methoxy-2- (3-methoxyphenyl)propylamιne The procedure described in the preparation of the starting compound 7) is followed to obtain the title compound as colourless solids Yield 72 % M p 85-86 °C (2-propanol, water) Analysis for C 2 ιHι 9 F 6 N0 3 (447 38) calculated C 56 38 %, H 4 28 %, N 3 13 %, found C 56 45 %, H 4 32 %, N 3 18 % IR (Kbr, cm "1 ) 3436, 1672, 1324, 1133 1 H-NMR (CDCI 3 400 MHz) δ 7 64 (1 H, d, J=15 6 Hz), 7 64-7 60 (4H, m), 7 35 (1 H, t, J=8 2 Hz), 7 10-7 06 (2H, m), 6 97-6 92 (1 H, m), 6 46 (1 H, d, J=15 6 Hz), 5 92 (1 H, bs), 4 27 (1 H, dd, J=14 9 Hz, J=5 4 Hz), 4 05 (1 H, ddq, J=14 9 Hz, J=5 4 Hz, J=1 1 Hz), 3 83 (3H, s), 3 40 (3H, s) 13 C-NMR (CDCI 3 100 6 MHz) δ 165 0, 159 9, 140 1 , 138 1 , 134 9, 131 4 (q, 2 J CF =32 8 Hz), 129 8, 128 0, 126 5 (q, 1 J CF =278 9 Hz), 125 8 (q, 3 J CF =3 8 Hz), 124 8 (q, 1 J CF =288 0 Hz), 122 5, 1 19 5, 1 14 5, 1 13 6, 80 7 (q, 2 J CF =26 7 Hz), 55 4, 52 7, 41 2 10) N-(4-Nιtrocιnnamoyl)-3,3,3-trιfluoro-2-methoxy-2-(3- methoxyphenyl)propylamιne The procedure described in the preparation of the starting compound 7) is followed to obtain the title compound as pale yellow solids Yield 64 % M p 80-81 °C (2-propanol, water) Analysis for C 20 Hι 9 F 3 N 2 O 5 (424 38) calculated C 56 61 %, H 4 51 %, N 6 60 %, found C 56 36 %, N 4 52 %, N 6 60 % IR (KBr, cm "1 ) 1659, 1515, 1345, 1 168, 1120 1 H-NMR (CDCI 3 200 MHz) δ 8 23 (2H, d, J=8 8 Hz), 7 67 (1 H, d, J=15 6 Hz), 7 65 (2H, d, J=8 8 Hz), 7 37 (1 H, t, J=8 2 Hz), 7 15-7 03 (2H, m), 7 00-6 90 (1 H, m), 6 55 (1 H, d, J=15 6 Hz), 6 02 (1 H, t, J=5 2 Hz), 4 30 (1 H, dd, J=15 0 Hz, J=5 5 Hz), 4 04 (1 H, ddq, J=15 0 Hz, J=5 5 Hz, J=1 6 HZ), 3 84 (3H, s), 3 40 (3H, s) 13 C-NMR (CDCI 3 50 3 MHz) δ 164 7, 159 9, 148 3, 140 9, 139 2, 134 8, 129 9, 128 5, 124 9 (q, 1 J CF =288 8 Hz), 124 3, 124.2, 1 19.5, 1 14.5, 1 13.6, 80.7 (q, 2 J CF =26.3 Hz), 55.3, 52.7, 41 .3. 1 1 ) The procedure described in the preparation of the starting compound 7) is followed to obtain the title compound as colourless solids. Yield: 85 %. M.p.: 104-106 °C (2-propanol, water). Analysis: for C 2 ιHi7F 6 N0 4 (461.36) calculated: C 54.67 %, H 3.71 %, N 3.04 %; found: C 54.46 %, H 3.70 %, N 3.05 %. IR (Kbr, cm "1 ): 3310, 1665, 1630, 1326, 1 170, 1 125. 1 H-NMR (CDCI 3 200 MHz) δ: 7.66 (1 H, d, J=15.4 Hz), 7.61 (4H, m), 7.05-6.95 (2H, m), 6.85 (1 H, d, J=7.7 Hz), 6.48 (1 H, d, J=15.4 Hz), 6.01 (2H, s), 5.96 (1 H, bs), 4.24 (1 H, dd, J=14.9 Hz, J=5.1 Hz), 4.04 (1 H, dd, J=14.9 Hz, J=5.1 Hz), 3.36 (3H, s). 13 C-NMR (CDCI 3 100.6 MHz) δ: 165.1 , 148.4, 148.2, 140.1 , 138.0 (q, 4 J CF =1 .5 Hz), 131 .3 (q, 2 J CF =32.4 Hz), 128.0, 126.8, 125.7 (q, 3 J CF =3.8 Hz), 124.8 (q, 1 J CF =288.0 Hz), 123.8 (q, 1 J CF =274.3 Hz), 122.5, 121 .2, 108.3, 107.9, 101 .48, 80.4 (q, 2 J CF =26.7 Hz), 52.4, 41 .0. 12) N-/2-(3,4-Methylenedioxyphenyl)ethyl/-4-trifluoromethyl- cinnamamide A solution of 4.6 g (0.023 moles) of (3,4-methylenedioxy- phenyl)ethylamine chlorohydrate in 50 cm 3 of ether is added to a solution of 4.1 g (0.2 moles) of sodium hydroxide in 30 cm 3 of water, drop by drop, at 5 to 10 °C under stirring Then, a solution of 4 2 g (0 02 moles) of 4-trιfluoromethylcιnnamoyl chloride in 20 cm 3 of ether is added to the mixture, drop by drop, in 35 minutes, and the reaction mixture is stirred for half an hour at 5 °C The precipitated carboxylic amide is filtered and dried Thus, 4 3 g (63 %) of the title product are obtained M p 206-208 °C 13) N-/2-(3,4-Methylenedιoxyphenyl)ethyl/-4-fluoro- cinnamamide A mixture of 4 84 g (0 029 moles) of (3,4-methylenedιoxy- phenyl)ethylamιne 4 98 g (0 03 moles) of 4-fluorocιnnamιc acid and 10 cm 3 of decahn is stirred at 180 °C for 1 hour To the cooled mixture, chloroform is added, and the mixture is stirred at 5 to 10 °C until the crystallization of the carboxylic amide The precipitated crystals are filtered, and recrystalhzed from ethanol Thus, 4 9 g (53 %) of the title product are obtained M p 160-162 °C 14) N-/3-(4-Trιfluoromethylphenyl)propanoyl/-3,3,3-trιfluoro- 2-methoxy-2-(3-methoxyphenyl)propylamιne A suspension of 1 25 g (5 mmoles) of 3,3,3-tπfluoro-2-methoxy- 2-(3-methoxyphenyl)propylamιne and 1 09 g (5 mmoles) of 3- (4-trιfluoromethylphenyl)propιonιc acid is reacted at 150 °C for 4 hours The crude product is recrystalhzed from aqueous ethanol Thus, 1 55 g (69 %) of colourless title compound are obtained M p 58-59 °C (ethanol-water) Analysis for C 2 ιH 2 ιF 6 N0 3 (449 40) calculated C 56 13 %, H 4 71 %, N 3 12 %, found C 56 16 %, H 4 74 %, N 3 09 % IR (KBr, cm '1 ) 3309, 1650, 1338, 1279 1 H-NMR (CDCI 3 200 MHz) δ 7 52 (2H, d, J=8 1 Hz), 7 35-7 25 (3H, m), 7 04-6 88 (3H, m), 5 62 (1 H, bs), 4 10 (1 H, dd, J=14 9 Hz, J=5 3 Hz), 3 85 (1 H, dd, J=4 4 Hz), 3 82 (3H, s), 3 24 (3H, s), 3 00 (2H, t, J=7 3 Hz), 2 50 (2H, t, J=7 3 Hz) 13 C-NMR (CDCI 3 100 6 MHz) δ 171 7, 159 8, 144 7, 134 7, 129 7, 128 7, 128 6 (q, 2 J CF =32 3 Hz), 125 4 (q, 3 J CF =3 7 Hz), 124 7 (q, 1 J CF = 288 6 Hz), 124 2 (q, 1 J CF =271 9 Hz), 119 4, 114 3, 113 5, 80 5 (q, 2 J CF =26 4 Hz), 55 3, 52 5, 41 0, 37 6, 31 0 15) N-/3-(4-Fluorophenylpropanoyl)-3,3,3-trιfluoro-2-methoxy- 2-(3-methoxyphenyl)propylamιne The procedure described in the preparation of the starting compound 14) is followed to obtain the title compound as colourless solids Yield 79 % M p 59-61 °C (ethanol-water) Analysis for C 20 H 21 F 4 NO 3 (399 39) calculated C 60 15 %, H 5 30 %, N 3 51 %, found C 59 93 %, H 5 28 %, N 3 52 % IR (KBr, cm "1 ) 3305, 1649, 151 1 , 1280 1 H-NMR (CDCI 3 200 MHz) δ 7 38-7 25 (1 H, m), 7 18-7 06 (2H, m), 7 05-6 87 (5H, m), 5 60 (1 H, bs), 4 09 (1 H, dd, J=14 8 Hz, J=5 1 Hz), 3 86 (1 H, dd, J=14 8 Hz, J=4 0 Hz), 3 82 (3H, s), 3 26 (3H, s), 2 90 (2H, t, J=7 5 Hz), 2 46 (2H, t, J=7 5 Hz) 13 C-NMR (CDCI 3 100 6 MHz) δ 171 7, 161 5 (d, 1 J CF =244 2 Hz), 159 8, 136 2 (d, 4 J C =3 4 Hz), 134 8, 129 7 (d, 3 J CF = 8 0 Hz), 129 7, 124 8 (q, 1 J CF =288 6 Hz), 1 19 4, 1 15 2 (d, 2 J CF =21 0 Hz), 1 14 4, 1 13 5 (q, 4 J CF =1 1 Hz), 80 5 (q, 2 J CF =26 3 Hz), 55 3, 52 5, 40 8, 38 2, 30 5 16) N-/3-(4-Trιfluoromethylphenyl)propanoyl/-3,3,3-trιfluoro- 2-methoxy-2-(3,4-methylenedιoxyphenyl)propylamιne The procedure described in the preparation of the starting compound 14) is followed to obtain the title compound as colourless solids Yield 84 % M p 75-76 °C (ethanol-water) Analysis for C 2 ιHι 9 F 6 N0 4 (463 38) calculated C 54 43 %, H 4 13 %, N 3 02 %, found C 54 52 %, H 4 19 %, N 3 05 % IR (KBr, cm '1 ) 3317, 1620, 1334, 1247 1 H-NMR (CDCI 3 200 MHz) δ 7 53 (2H, d, J=7 7 Hz), 7 30 (2H, d, J=7 7 Hz), 7 00-6 80 (3H, m), 6 00 (2H, s), 4 06 (1 H, dd, J=14 9 Hz, J=5 1 Hz), 3 84 (1 H, dd, J=14 9 Hz, J=5 1 Hz), 3 21 (3H, s), 3 01 (2H, t, J=7 5 Hz), 2 51 (2H, t, J=7 5 Hz) 13 C-NMR (CDCI 3 100 6 MHz) δ 171 4, 148 3, 148 1 , 144 7, 128 7 (q, 2 J CF =32 4 Hz), 128 7, 126 8, 125 4 (q, 3 J C F=3 7 Hz), 124 7 (q, 1 J CF =288 4 Hz), 124 2 (q, 1 J CF =271 7 Hz), 121 1 , 108 2, 107 8, 101 5, 80 3 (q, 2 J CF =26 4 Hz), 52 2, 40 7, 37 7, 31 1 17) N-/3-(4-Fluorophenyl)propanoyl/-3,3,3-trιfluoro-2-methoxy- 2-(3,4-methylenedιoxyphenyl)propylamιne The procedure described in the preparation of the starting compound 14) is followed to obtain the title compound as colourless solids Yield 83 % M p 92-94 °C (ethanol-water) Analysis for C 20 Hι 9 F 4 NO 4 (413 37) calculated C 58 1 1 %, H 4 63 %, N 3 39 %, found C 58 29 %, H 4 67 %, N 3 41 %, IR (KBr, cm 1 ) 3325, 1658, 1510, 1217 H-NMR (CDCI 3 200 MHz) δ 7 18-7 10 (2H, m), 7 02-6 75 (5H, m), 6 00 (2H, s), 5 61 (1 H, bs), 4 06 (1 H, dd, J=14 7 Hz, J=5 9 Hz), 3 85 (1 H, dd, J=14 7 Hz, J=4 2 Hz), 3 23 (3H, q, J=0 7 Hz), 2 92 (2H, t, J=7 5 Hz), 2 51 (2H, t, J=7 5 Hz) 13 C-NMR (CDCI 3 50 3 MHz) δ 171 7, 161 6 (d, 2 J CF =244 1 Hz), 148 3, 148 1 , 136 2 (d, 4 J CF =3 4 Hz), 129 7 (d, 4 J CF =3 4 Hz), 129 7 (d, 3 J CF =7 6 Hz), 126 8, 124 7 (q, 1 J CF =288 4 Hz), 121 2, 1 15 2 (d, 2 J CF =21 4 Hz), 108 2, 107 8, 101 5, 80 3 (q, 2 J CF =26 5 Hz), 52 2, 40 6, 38 2, 30 5 18) N-/2-(3,4-Methylenedιoxyphenyl)ethyl/- 4-tπfluoromethyl- cinnamamide A solution of 4 6 g (0 023 moles) of (3,4-methylenedιoxy- phenyl)ethylamιne chlorohydrate in 50 cm 3 of ether is added to a solution of 4 1 g (0 2 moles) of sodium hydroxide in 30 cm 3 of water, drop by drop, at 5 to 10 °C under stirring Then, a solution of 4 2 g (0 02 moles) of 4-trιfluoromethylcιnnamoyl chloride in 20 cm 3 of ether is added to the mixture, drop by drop, in 35 minutes, and the reaction mixture is stirred for half an hour at 5 °C The precipitated carboxylic amide is filtered and dried Thus 4 3 g (63 %) of the title product are obtained M p 206-208 °C 19) N-/2-(3,4-Methylenedιoxyphenyl)ethyl/cιnnamamιde To a solution of 8 5 g (0 037 moles) of (3,4-methylenedιoxy- phenyl)ethylamιne in 50 cm 3 of dichloromethane, 5 g of sodium hydrogen carbonate are added, then a solution of 6 2 g (0 037 moles) of cinnamoyl chloride in 20 cm 3 of dichloromethane is added in half an hour The reaction mixture is stirred at 40 °C for 2 hours, then filtered, and the dichloromethane is evaporated Thus, 10 6 g (96 %) of the title compound are obtained in the form of an oil 20) N-/2-(3,4-Ethylenedιoxyphenyl)ethyl/-3-(4-trιfluoromethyl- phenyl)propιonyl amide 14 3 g (0 08 moles) of (3,4-ethylenedιoxy-phenyl)ethylamιne and 18 4 g (0 08 moles) of 3-(4-trιfluoromethylphenyl)propιonιc acid are heated in 20 cm 3 of decahn to 160-170 °C, and the reaction mixture is stirred at this temperature for 4 hours The water formed is distilled off The mixture is cooled to 60 °C, and 50 cm 3 of ethanol is added under intensive stirring The suspension cooled to 10 °C is filtered, washed with some cold ethanol Thus, 17 2 g (56 %) of the title compound are obtained as crude product M p 161 -163 °C 21 ) N-/2-(3,4-Methylenedιoxyphenyl)ethyl/-4-fluoro- cinnamamide A mixture of 4 84 g (0 029 moles) of (3,4-methylenedιoxy- phenyl)ethylamιne, 4 98 g (0 03 moles) of 4-fluorocιnnamιc acid and 10 cm 3 of decahn is stirred at 180 °C for 1 hour To the cooled mixture, chloroform is added, and the mixture is stirred at 5 to 10 °C until the crystallization of the carboxylic amide The precipitated crystals are filtered, and recrystalhzed from ethanol Thus, 4 9 g (53 %) of the title product are obtained M p 160-162 °C 22) N-/2-(4-Chlorophenylethyl)-3-(4-trιfluoromethylphenyl)- propionyl amide 7 8 g (0 05 moles) of (4-chlorophenyl)ethylamιne and 10 5 g (0 05 moles) of 4-tπfluoromethylcιnnamιc acid are heated in 25 cm 3 of decahn to 180 °C and stirred at this temperature for 14 hours To the mixture cooled to room temperature, 50 cm 3 of diethyl ether are added in portions The crystalline carboxylic amide obtained is filtered and washed with ether Thus, 14 g (79 %) of the title compound are obtained as crude product M p 167-168 °C 23) N-/2-(3,4-Ethylenedιoxyphenyl)-2-propylethyl/-3-(4-trι- fluoromethylphenyl)propιonyl amide 11 0 g (0 05 moles) of 2-(3,4-ethylenedιoxyphenyl)-2- propylethylamine and 10 9 g (0 05 moles) of 3-(4-tπfluoro- methylphenyl)propιonιc acid are heated to 160 °C, and the melt obtained is stirred at this temperature for 4 hours The water that forms is distilled off The mixture is cooled to 0-5 °C, and the precipitated crystalline product is filtered The crude product is purified by column chromatography Thus, 10 g (47 %) of the title compound are obtained in the form of yellow resin 24) N-/2-(3,4-Methylenedιoxyphenyl)ethyl/-3-(4-trιfluoro- methylphenyl)propιonyl amide A solution of 3 63 g of N-/2-(3,4-methylenedιoxyphenyl)ethyl/-4- tnfluoromethylcinnamamide in 100 cm 3 of acetic acid is hydrogenized in the presence of 1 g of palladium/carbon catalyst at atmospheric pressure until the end of the hydrogen consumption The catalyst is filtered, and the solution is evaporated to dryness The crude product is recrystalhzed from acetone 25) N-/2-(3,4-Ethylenedιoxyphenyl)-2-propylethyl/-4-(tπfluoro- methyl)cιnnamamιde 12 3 g (55 mmoles) of 2-(3,4-ethylenedιoxyphenyl)-2-propyl- ethylamine and 12 0 g (55 mmoles) of 4-trιfluoromethylcιnnamιc acid are heated in 100 cm 3 of deca n to 160-165 °C The mixture is stirred at the above temperature for 2 hours, then cooled to room temperature The solvent is removed by decantation, from the residue 50 cm 3 of toluene are distilled off, and the brownish crude product is purified by column chromatography Thus, 12 1 g (52 %) of the title compound are obtained in the form of thick oil that solidifies Preparation of the starting compounds of the formula XII: 26) 6,7-Ethylenedιoxy-1 -/2-(4-trιfluoromethylphenyl)ethyl/- 3,4-dιhydroιsoquιnohne 14 2 g (0 037 moles) of 2-(3,4-ethylenedιoxyphenyl)ethyl-N-/3- (4-trιfluoromethylphenyl)/propιonyl amide are dissolved in 80 cm3 of toluene To the solution obtained, 12 cm 3 of phosphor(V) trichloride oxide are added, drop by drop, the reaction mixture is heated to 80 °C and stirred at this temperature for 2 5 hours The precipitated crystalline dihydroisoquinohπe is filtered and recrystalhzed from ethanol The product obtained (12 g) is dissolved in 90 cm 3 of methanol, made alkaline to pH 9 by the addition of 20 % aqueous sodium hydroxide solution, the precipitated matter is filtered, washed with aqueous methanol (5 1 ), and recrystalhzed from a mixture of ethanol and water Thus, 1 44 g (41 %) of the title compound are obtained M p 85 °C Analysis for C 20 Hι 8 NO 2 (361 37) calculated C 66 48 %, H 5 02 %, N 3 88 %, found C 66 34 %, H 5 04 %, N 3 90 % 1 H-NMR (CDCI 3 400 MHz) δ 7 61 (2H, d, J=8 0 Hz), 7 47 (2H, d, J=8 0 Hz), 7 10 (1 H s), 6 74 (1 H, s), 4 24 (4H, m), 3 48 (2H, t, J=7 4 Hz), 2 96 (4H, m), 2 47 (2H, t, J=7 1 Hz) 27) 1 -(2-Phenylethyl)-6,7-methylenedιoxy-3,4-dιhydro- isoquinohne A solution of 10 g (0 033 moles) of N-/2-(3,4-methylenedιoxy- phenyl)ethyl/-3-phenylpropιonyl amide and 30 cm 3 of phosphor(V) trichloride oxide in 70 cm 3 of absolute benzene is boiled for 1 5 hours, then cooled to 50 °C, and the precipitated crystals are filtered The crude hydrochloπde is dissolved in a mixture of 200 cm 3 of water and 200 cm 3 of methanol, the pH value of the solution is adjusted to 13 by the addition of 20 % aqueous sodium hydroxide solution The precipitated white crystalline base is filtered, washed with cold water, dried, and recrystalhzed from a mixture of ethanol and water Thus, 5 3 g (58 %) of the title compound are obtained M p 112-115 °C Preparation of the starting compounds of the formula XVI: 28) α,α,α-Trιfluoro-3-methoxyacetophenone To a solution of 35 52 g (0,25 mmoles) of ethyl tnfluoroacetate in 100 cm 3 of tetrahydrofuran, a solution of 3-methoxyphenyl magnesium bromide /prepared from 46 76 g (0 25 moles) of 3- bromoanisole, 6 32 g (0 26 moles) of magnesium and 200 cm 3 of tetrahydrofuran in the usual manner/ is added slowly at -70 °C, drop by drop The reaction mixture is stirred at -70 °C for an hour, than allowed to warm to 0 °C Then, 100 cm 3 of 2N hydrochloric acid are added slowly to the reaction mixture, drop by drop The mixture is stirred for half an hour, the two phases are separated The tetrahydrofuran phase is dried over anhydrous magnesium sulfate, the solvent is evaporated The crude product is fractionated under reduced pressure At a pressure of 1600 Pa, the fraction from 83 to 85 °C is collected Thus, 39 81 g (78 %) of the title compound are obtained 1 H-NMR (CDCI 3 , 250 MHz) δ 7 70-7 20 (4H, m), 3 88 (3H, s) literature value 1 H-NMR δ 7 72-7 16 (4H, m), 3 81 (3H, s) 29) α,α,α-Tπfluoro-3,4-methylenedιoxyacetophenone The title compound is prepared in a similar manner as the starting compound under 28) The crude product is fractionated under reduced pressure At a pressure of 373 Pa, the fraction from 84 to 85 °C is separated Yield 63 % Analysis for C 9 H 5 F 3 0 3 (218 134) calculated C 49 56 %, H 2 31 %, found C 49 43 %, H 2 20 % IR (KBr, cm 1 ) 1702, 1614, 1364 H-NMR (CDCI 3 , 250 MHz) δ 7 68 (1 H, dd, J=8 3 Hz, J=1 2 Hz), 7 45 (1 H, d, J=1 2 Hz), 6 90 (1 H, d, J=8 3 Hz), 6 10 (2H, s) Preparation of starting compounds of the formula XV: 30) 3,3,3-Trιfluoro-2-methoxy-2-(3-methoxyphenyl)propιonιtrιle A suspension of 61 25 g (0 3 moles) of α,α,α-trιfluoro-3- methoxyacetophenone, 150 cm 3 of 1 ,2-dιmethoxyethane and 32 56 g (0 50 moles) of potassium cyanide is stirred at room temperature for 15 minutes To the reaction mixture, 50 45 g (38 0 cm 3 , 0 40 moles) of dimethyl sulfate are added, drop by drop, the mixture is stirred at 60 °C for 5 minutes, then allowed to stand for a night The mixture is filtered, from the mother liquor, the solvent is distilled off The crude product is fractionated under reduced pressure At a pressure of 933 Pa, the fraction from 80 to 82 °C is separated Thus, 60 0 g (82 %) of the title compound are obtained Analysis for CnH 10 F 3 NO 2 (245 20) calculated C 53 88 %, H 4 11 %, N 5 71 %, found C 53 50 %, H 4 10 %, N 5 51 % IR (film, cm "1 ) 2850, 2250, 1190 1 H-NMR (CDCI 3 , 250 MHz) δ 7 41 , (1 H, t, J=8 0 Hz), 7 30-7 00 (3H, m), 3 83 (3H, s), 3 49 (3H, s) 31 ) 3,3,3-Trιfluoro-2-methoxy-2-(3,4-methyleπedιoxyphenyl)- propionitnle 32 72 g (0 15 moles) of α, ,α-trιfluoro-3,4-methylenedιoxy- acetophenone are dissolved in 330 cm 3 of 1 ,2-dιmethoxy- ethane, and the solution is stirred with 14 70 g (0 30 moles) of sodium cyanide for 15 minutes To the suspension formed, 20 73 g (0 15 moles) of potassium carbonate are added, and to the reaction mixture 42 7 cm 3 (56 76 g, 0 45 moles) of dimethyl sulfate are added, drop by drop, and the mixture is stirred at room temperature for 3 hours Then, to the mixture cooled to 0 °C, 42 cm 3 of 25 % aqueous ammonia solution are added, drop by drop The mixture is diluted with 330 cm 3 of water and extracted twice with 160 cm 3 of ethyl acetate each time The combined organic phases are washed twice using 160 cm 3 of saturated aqueous sodium chloride solution each time and dried over anhydrous magnesium sulfate The solvent is distilled off Since the residue contains about 20 % of the starting cetone, the above steps are repeated using identical amounts of substances to obtain a more complete conversion The crude product is purified by fractionation under reduced pressure using a Vigreux column At a pressure of 40 Pa, the fraction from 78 to 88 °C is collected Thus, 27 60 g (71 %) of the title compound are obtained Analysis for CnH 8 F 3 N0 3 (259 19) calculated C 50 98 %, H 3 11 %, N 5 40 %, found C 50 75 %, H 3 17 %, N 5 45 % IR (film, cm '1 ) 2909, 2248, 1492, 1254, 1189 1H-NMR (CDCI 3 , 200 MHz) δ 7 17 (1 H, dd, J=8 1 Hz, J=1 8 Hz), 7 05 (1 H, d, J=1 8 Hz), 6 89 (1 H, d, J=8 1 Hz), 6 05 (2H, s), 3 48 (3H, s) Preparation of starting compounds of the formula X: 32) 3,3,3-Trιfluoro-2-methoxy-2-(3-methoxyphenyl)propyl- amine To a suspension of 24 52 g (0 10 moles) of 3,3,3-trιfluoro-2- methoxy-2-(3-methoxyphenyl)propιonιtrιle, 23 78 g (0 10 moles) of cobalt(ll) chloride hexahydrate and 250 cm 3 of methanol, 3 78 g (0 10 moles) of sodium tetrahydroborate(lll) are added in several portions at 0 °C The reaction mixture is stirred at room temperature and allowed to stand for a night The solvent is distilled off, and the residue is suspended in 500 cm 3 of water The unreacted sodium tetrahydroborate(lll) is hydrohzed with 2N hydrochloric acid solution Then the pH is adjusted to 13 with 20 % aqueous sodium hydroxide solution The mixture is extracted three times using 300 cm 3 of dichloromethane each time The combined organic phases are dried over anhydrous magnesium sulfate The solvent is evaporated The residue is fractionated under reduced pressure At a pressure of 533 Pa, the fraction from 103 to 104 °C is collected Thus, 15 20 g (61 %) of the title compound are obtained Analysis for CnH 14 F 3 N0 2 (249 23) calculated C 53 01 %, H 5 66 %, N 5 62 %, found C 52 65 %, H 5 53 %, N 5 78 % IR (film, cm '1 ) 2800, 1 174, 1119 1 H-NMR (CDCI 3 , 250 MHz) δ 7 33 (1 H, t, J=8 2 Hz), 7 05 (2H, m), 6 90 (1 H, ddd, J=8 2 Hz, J=2 5 Hz, J=0 8 Hz), 3 82 (3H, s), 3 42 (3H, s), 3 36 (1 H, d, J=14 6 Hz), 3 13 (1 H, d, J=14 6 Hz), 1 20 (2H, s) 13 C-NMR (CDCI 3 , 62 9 Mhz) δ 159 7, 135 8, 129 4, 125 4 (q, 1 J C =289 6 Hz), 1 19 2, 113 5, 82 2 (q, 2 J CF =24 8 Hz), 54 9, 52 5, 45 7 Preparation of the hydrochloπde 12 46 g (50 mmoles) of the base 3,3,3-trιfluoro-2-(3-methoxy- phenyl)propylamιne are dissolved in 125 cm 3 of diethyl ether, and, to the solution obtained, 8 6 cm 3 of 2-propanol containing (60 mmoles, 25 3 g/100 cm 3 ) of hydrogen chloride are added, drop by drop The precipitated crystals are filtered, washed with 30 cm 3 of diethyl ether Thus, the hydrochlonde of the title compound (12 28 g, 86 %) are obtained M p 219-220 °C (2- propanol, diethyl ether) Analysis for CnHi 5 CIF 3 N0 2 (285 69) calculated C 46 25 %, H 5 29 %, Cl 12 41 %, N 4 90 %, found C 45 92 %, H 5 15 %, Cl 12 72 %, N 4 98 % IR (film, cm "1 ) 2945, 1502, 1130 1 H-NMR (DMSO-d 6 , 250 MHz) δ 8 47 (3H, s), 7 44 (1 H, t, J=7 9 Hz), 7 10 (3H, m), 3 96 (1 H, t, J=14 8 Hz), 3 80 (3H, s), 3 61 (1 H, t, J=14 8 Hz), 3 30 (3H, s) 33) 3,3,3-Tπfluoro-2-methoxy-2-(3,4-methylenedιoxyphenyl)- propylamine The title compound is prepared in a similar manner as the starting compound under 32) The crude product is fractionated under reduced pressure At a pressure of 147 Pa, the fraction from 1 14 to 1 16 °C is collected Yield 68 % The title compound is a colourless oil Analysis for CnHι 2 F 3 N0 3 (263 22) calculated C 50 19 %, H 4 60 %, N 5 32 % found C 49 96 %, H 458 %, N 5 34 % IR (film, cm 1 ) 2951 , 1492, 1167 1 H-NMR (CDCI 3 , 200 MHz) δ 6 97 (1 H, m), 6 93 (1 H, ddd, J=8 2 Hz, J=1 8 Hz, J=0 4 Hz), 6 83 (1 H, dd, J=8 2 Hz J=0 4 Hz), 5 97 (2H, s), 3 39 (3H, q, J=1 2 Hz), 3 36 (1 H, d, J=14 6 Hz), 3 12 (1 H, dq, J=14 6 Hz, J=1 6 Hz), 1 28 (2H, bs) 13 C-NMR (CDCI 3 , 100 6 MHz) δ 147 9, 147 7, 127 8, 125 3 (q, 1 J CF =289 5 Hz), 120 8 (q, J=1 5 Hz), 108 0, 107 7 (q, J=1 5 Hz), 101 2, 82 0 (q, 2 J CF =24 8 Hz), 52 3 (q, J=289 6 Hz), 45 3 (q, 3 J CF = 1 1 Hz) Preparation of the hydrochloπde A similar procedure is followed as in the preparation of the hydrochloπde under 32) Yield 81 % M p 248-249 °C Analysis for CnH 13 CIF 3 N0 3 (299 68) calculated C 44 09 %, H 4 37 %, Cl 11 83 %, N 4 67 %, found C 44 31 %, H 4 40 %, Cl 11 81 %, N 4 65 % IR (film, cm "1 ) 2925, 1449, 1 112, 1076 1H-NMR (DMSO-d 6 , 400 MHz) δ 8 55 (3H, bs), 7 1 (1 H„ s), 7 05-7 02 (2H m), 6 10 (2H, s), 3 90 (11-1, d, J=14 9 Hz), 3 57 (1 H, d, J=14 9 Hz), 3 29 (3H, s) Example 1 6-Methoxy-1 -styryl-4-trιfluoromethyhsoquιnohne Method A) To a solution of 1 19 g (3 mmoles) of 4,6-dιmethoxy-1 -styryl-4- trιfluoromethyl-3,4-dιhydroιsoquιnohnιum chloride in 10 cm 3 of methanol, 0 42 g (7 5 mmoles) of powdered potassium hydroxide are added at 0 °C, and the reaction mixture, is stirred at room temperature for 2 hours The mixture is evaporated, the residue is rubbed with 10 cm 3 of water,, then filtered The crystals are washed with 5 cm 3 of water, then twice with 3 cm 3 of ethanol each time at 0 °C Thus, 0 94 g (95 %) of the title compound are obtained in the form of pale yellow matter M p 202-203 °C (chloroform) Method B) A suspension of 2 73 g (10 mmoles) of 1 -methyl-4,6-dιmethoxy- 4-trιfluoromethyl-3,4-dιhydroιsoquιnohne, 1 17 g (11 mmoles) of benzaldehyde and 1 33 g (13 mmoles) of acetic anhydride is reacted at 100 °C for 16 hours The precipitated crystals are filtered, washed twice with 5 cm 3 of ethanol each time at 0 °C Thus, 2 14 g (65 %) of the title compound are obtained M p 202-203 °C (chloroform) Method C) A suspension of 2 41 g (10 mmoles) of 1 -methyl-6-methoxy-4- tπfluoromethylisoquinoline, 1 17 g (11 mmoles) of benzaldehyde and 1 33 g (13 mmoles) of acetic anhydride is reacted at 100 °C for 16 hours The precipitated crystals are filtered, washed twice with 5 cm 3 of ethanol at 0 °C each time Thus, 1 98 g (60 %) of the title compound are obtained M p 202-203 °C (chloroform) Analysis for Cι 9 Hι 4 F 3 NO (329 32) calculated C 69 20 %, H 4 28 %, N 4 25 %, found C 69 02 %, H 4 25 %, N 4 20 % IR (KBr, cm 1 ) 1619, 141 1 , 1318, 1221 , 1 100 1 H-NMR (CDCI 3 , 200 MHz) δ 8 79 (1 H, s), 8 36 (1 H, d, J=9 5 Hz), 8 07 (1 H, d, J=15 8 Hz), 7 92 (1 H, d, J=15 8 Hz), 7 75-7 65 (2H, m), 7 45-7 30 (5H, m), 3 99 (3H, s) 13 C-NMR (CDCI3, 50 3 MHz) δ 161 7 157 8, 141 1 (q, 3 J CF =6 5 Hz), 138 7, 136 3, 135 0, 129 3, 128 9, 127 7, 127 1 , 124 8 (q, 1 J CF =273 1 Hz), 121 8, 120 5, 1 17 8 (q, 2 J CF =30 1 Hz), 102 1 , 55 6 MS (m/z, %) 329 (37), 328 (100), 314 (7), 310 (3), 298 (8), 286 (10), 285(37), 252(7) 6-Methoxy-1 -styryl-4-trιfluoromethyhsoquιnolιnιum chloride 0 99 g (3 mmoles) of the above base are reacted with 0 5 cm 3 of 2-propanol containing 3 6 mmoles (25 3 g/100 cm 3 ) of hydrogen chloride Thus, 0 74 g (67 %) of the title hydrochlonde are obtained in the form of pale yellow matter M p 189-190 °C (ethanol, dnsopropyl ether, decomposition) Analysis for d 9 Hι 5 CIF 3 NO (365 78) calculated C 62 39 %, H 4 13 %, Cl 9 69 %, N 3 83 %, found C 62 21 %, H 4 17 %, Cl 9 60 %, N 3 86 % IR (film, cm "1 ) 1618, 1240 1 H-NMR (DMSO-d 6 , 250 MHz) δ 8 92 (1 H, d, J=9 4 Hz), 8 76 (1 H, s), 8 28 (11-1, d, J=I5 7 Hz), 8 15 (1 H, d, J=15 7 Hz), 7 93- 7 89 (2H, m), 7 58 (1 H, d, J=9 4 Hz), 7 50-7 40 (3H, m), 7 32 (1 H, s), 4 00 (3H, s) Example 2 1 -(4-Fluorostyryl)-6-methoxy-4-tπfluoromethyhsoquιnohne Method A) 1 14 g (3 mmoles) of 1 -(4-fluorostyryl)-4,6-dιmethoxy-4-tπfluoro- methyl-3,4-dιhydroιsoquιnohne are dissolved in a mixture of 20 cm 3 of toluene and 10 cm 3 of methanol To the solution formed, 0 25 g (4 5 mmoles) of powdered potassium hydroxide are added at 0 °C, the reaction mixture is stirred at room temperature for 2 hours, then evaporated The residue is rubbed with 10 cm 3 of water, and filtered The crystals are washed with 5 cm 3 of water, then twice with 3 cm 3 of ethanol at 0 °C each time Thus, 0 92 g (93 %) of the title compound are obtained in the form of pale yellow matter M p 187-188 °C (chloroform) Method B) The procedure described in Example 1 , method B) is followed Yield 64 % M p 188-189 °C (chloroform) Method C) The procedure described in Example 1 , method C) is followed Yield 63 % M p 188-189 °C (chloroform) Analysis for Cι 9 Hι 3 F 4 NO (347 32) calculated C 65 71 %, H 3 77 %, N 4 03 %, found C 65 84 %, H 3 79 %, N 4 08 % IR (KBr, cm "1 ) 1618 1510, 1321 , 1275 1130 1 H-NMR (CDCI 3 , 250 MHz) δ 8 77 (1 H, s), 8 31 (1 H, d, J=9 1 Hz), 8 01 (1 H, d, J=15 5 Hz), 7 81 (1 H, d, J=15 5 Hz), 7 70-7 63 (2H, m), 7 35-7 29 (2H, m), 7 1 1 (2H, t, J=8 7 Hz), 3 98 (3H, s) 13 C-NMR (CDCI 3 62 9 MHz) δ 165 2, 161 5, 159 5 (d, 1 J CF =221 5 Hz), 141 3 (q, 3 J CF =6 6 Hz), 136 9, 134 8, 132 6, 129 3, 129 2, 126 8, 124 8 (q, 1 J CF =273 6 Hz), 121 8, 120 3, 117 7 (q, 2 J CF =29 3 Hz), 1 15 8 (d, 2 J CF =21 0 Hz), 102 1 , 55 4 MS (m/z, %) 347 (34), 346 (100), 332 (10), 328 (4), 316 (9), 304 (10), 303 (34), 252 (8) 1 -(4-Fluorostyryl)-6-methoxy-4-trιfluoromethyhsoquιnohnιum chloride 1 04 g (3 mmoles) of the above base are reacted with 0 5 cm 3 of 2-propanol containing 3 6 mmoles (25 3 g/100 cm 3 ) of hydrogen chloride Thus, 0 63 g (72 %) of the title hydrochloπde are obtained M p 189-190 °C (ethanol, decomposition) Analysis for Cι 9 Hι 4 CIF 4 NO (383 77) calculated C 59 46 %, H 3 68 %, Cl 9 24 %, N 3 65 %, found C 59 19 %, H 3 72 %, Cl 9 10 %, N 3 58 % IR (film, cm 1 ) 3437, 1615, 1228, 1 162 1 H-NMR (DMSO-d 6 , 250 MHz) δ 8 95 (1 H, d, J=9 5 Hz), 8 77 (1 H, s), 8 29 (1 H, d, J=15 6 Hz), 8 18 (1 H, d, J=15 6 Hz), 8 04 (1 H, d, J=5 6 Hz), 8 00 (1 H, d, J=5 6 Hz), 7 56 (1 H, dd, J=9 4 Hz, J=2 4 Hz), 7 33 (2H, t, J=8 8 Hz), 7 29 (1 H, s), 4 02 (3H, s) Example 3 6-Methoxy-4-trιfluoromethyl-1 -(4-trιfluoromethylstyryl)- isoquinolme Method A) The procedure described in Example 1 , method A) is followed to obtain the title compound as pale yellow solids Yield 90 % M p 160-161 °C (chloroform) Method B) The procedure described in Example 1 , method B) is followed to obtain the title compound Yield 62 % M p 160-161 °C (chloroform) Method C) The procedure described in Example 1 , method C) is followed to obtain the title compound Yield 70 % M p 160-161 °C (chloroform) Analysis for C 20 Hι 3 F 6 NO (397 32) calculated C 60 46 %, H 3 30 %, N 3 53 %, found C 60 70 %, H 3 27 %, N 3 63 % IR (KBr, cm "1 ) 1620, 1409, 1324, 1121 1 H-NMR (CDCI 3 , 250 MHz) δ 8 80 (1 H, s), 8 34 (1 H, d, J=9 7 Hz), 8 08 (1 H, d, J=15 6 Hz), 7 98 (1 H, d, J=15 6 Hz), 7 78 (2H, d, J=8 3 Hz), 7 68 (2H, d, J=8 3 Hz), 7 37 (1 H, s), 7 35 (1 H, dd, J=9 7 Hz, J=2 5 Hz), 4 00 (3H, s) 13 C-NMR (CDCI 3 62 9 MHz) δ 161 7, 157 2, 141 4 (q, 3 J CF =6 5 Hz), 139 8, 136 5, 135 0, 130 1 (q, 2 J CF =32 5 Hz), 127 8, 126 8, 125 8 (q, 3 J C F=4 6 Hz), 124 8 (q, 1 J CF =271 8 Hz), 124 5, 124 2 (q, 1 J CF =271 0 Hz), 122 6, 120 8, 1 18 5 (q, 2 J CF =27 8 Hz), 102 1 , 55 6 MS (m/z, %) 397 (57), 396 (100), 382 (11), 378 (9), 366 (12), 354 (10), 353 (36), 328 (6), 285 (11), 252 (16), 69 (8) 6-Methoxy-4-trιfluoromethyl-1 -(4-trιfluoromethylstyryl)- isoquino nium chloride 1 19 g (3 mmoles) of the above base are reacted with 0 5 cm 3 of 2-propanol containing 3 6 mmoles (25 3 g/100 cm 3 ) of hydrogen chloride Thus, 0 72 g (66 %) of the yellow title hydrochlonde are obtained M p 189-190 °C (ethanol, decomposition) Analysis for C 20 Hι 4 CIF 6 NO (433 78) calculated C 55 38 %, H 3 25 %, Cl 8 17 %, N 3 23 %, found C 55 62 %, H 3 37 %, Cl 8 29 %, N 3 19 % IR (film, cm 1 ) 3433, 1613, 1319, 1 132 1 H-NMR (DMSO-d 6 , 250 MHz) δ 8 92 (1 H, d, J=9 5 Hz), 8 83 (1 H, s), 8 47 (1 H, d, J=15 5 Hz), 8 20-8 13 (3H, s), 7 81 (2H, d, J=8 2 Hz), 7 54 (1 H, dd, J=9 5 Hz, J=2 4 Hz), 7 29 (1 H, s), 4 00 (3H, s) 2-Methyl-6-methoxy-4-trιfluoromethyl-1 -(4-tπfluoromethylstyryl)- isoquinohnium iodide A mixture of 1 00 g (2 5 mmoles) of the above base and 10 cm 3 of methyl iodide are boiled for 40 hours The precipitated crystals are filtered, the crude product is recrystal zed^from ethanol Thus, 0 78 g (58 %) of the title quaternary salt are obtained in the form of orange yellow solids M p 213-215 °C (ethanol) Analysis for C 2 ιHι 6 F 6 INO (539 26) calculated C 46 77 %, H 2 99 %, N 2 60 %, found C 46 55 %, H 2 97 %, N 2 64 % IR (KBr, cm 1 ) 3035, 1616 1324, 1249, 1 170 1130 1 H-NMR (DMSO-d 6 , 400 MHz) δ 9 29 (1 H, s), 8 69 (1 H, d, J=9 5 Hz), 8 12 (2H, d, J=8 2 Hz), 7 94 (1 H, d, J=16 4 Hz), 7 92 (2H, d, J=8 2 Hz), 7 78 (1 H, dd, J=9 5 Hz, J=2 9 Hz), 7 47 (1 H, d, J=16 4 Hz), 7 46 (1 H, s), 4 36 (3H, s), 4 14 (3H, s) 13 C-NMR (DMSO-d 6 100 6 MHz) δ 166 5, 160 0, 144 7, 138 5 (q), 137 5 (q, 3 J CF =6 9 Hz), 135 3, 134 5, 130 4 (q, 2 J CF =31 9 Hz), 129 3, 126 0 (q, 3 J CF =3 8 Hz), 124 1 (q, 1 J CF =272 1 Hz), 123 5, 122 9 (q, 1 J CF =273 7 Hz), 122 7, 1 19 8, 1 19 4 (q, MS (m/z, %) 397 (48), 396 (74), 382 (18), 378 (10), 366 (18), 354 (12), 353 (33), 328 (4), 285 (10), 252 (15), 142 (100), 127 (39), 69 (5) Example 4 6-Methoxy-1 -(4-πιtrostyryl)-4-tπfluoromethyhsoquιnolιne Method A) The procedure described in Example 1 , method A) is followed to obtain the title compound as lemon-yellow solids Yield 92 %) M p 223-224 °C (chloroform) Method B) The procedure described in Example 1 , method B) is followed to obtain the title compound Yield 74 % M p 222-223 °C (chloroform) Method C) The procedure described in Example 1 method C) is followed to obtain the title compound Yield 73 % M p 222-223 °C (chloroform) Analysis for Cι 9 Hι 3 F 3 N 2 0 3 (374 32) calculated C 60 97 %, H 3 50 %, N 7 48 %, found C 60 78 %, H 3 46 %, N 7 46 % IR (KBr, cm "1 ) 1619, 1327, 1106 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 92 (1 H, d, J=9 3 Hz), 8 87 (1 H, s), 8 56 (1 H, d, J=15 3 Hz), 8 29 (2H, d, J=8 7 Hz), 8 21 (2H, d, J=8 7 Hz), 8 18 (1 H, d, J=15 3 Hz), 7 55 (1 H, d, J=9 3 Hz), 7 30 (11-1, s), 4 00 (3H, s) 13 C-NMR (CDCI 3 50 3 MHz) δ 161 9, 157 4, 147 5, 142 8, 135 7, 134 2, 129 3, 128 7, 127 0, 126 2 (q, 1 J CF =274 3 Hz), 124 1 , 121 8, 120 7, 1 16 4 (q, 2 J CF =32 7 Hz), 101 7, 55 9 MS (m/z, %) 374 (100), 373 (99), 359 (12), 355 (7), 344 (12), 343 (28) 328 (27), 327 (68), 326 (15), 313 (15), 285 (29), 284 (23), 283 (16), 252 (26), 216 (12), 215 (19) 6-Methoxy-1 -(4-nιtrostyryl)-4-trιfluoromethylιsoquιnolιnιum chloride 1 12 g (3 mmoles) of the above base are reacted with 0 5 cm 3 of 2-propanol containing 3 6 moles (25 3 g/100 cm 3 ) of hydrogen chloride Thus, 0 86 g (70 %) of the title hydrochloπde are obtained in the form of light yellow solids M p above 250 °C (ethanol) Analysis for C 19 Hι 4 CIF 3 N 2 0 3 (410 78) calculated C 55 56 % H 3 44 %, Cl 8 63 %, N 6 82 %, found C 55 87 %, H 3 29 % Cl 8 56 %, N 6 84 % IR (film, cm 1 ) 2440, 1646, 1345, 1262 1 H-NMR (DMSO-de, 200 MHz) δ 8 96 (1 H, d, J=9 5 Hz), 8 86 (1 H, s), 8 57 (1 H, d, J=I5 4 Hz), 8 36-8 14 (5H, m), 7 57 (1 H, dd, J=9 5 Hz, J=2 2 Hz), 7 30 (1 H, s), 3 85 (3H, s) Example 5 6,7-Methylenedιoxy-4-tπfluoromethyl-1 -(4-trιfluoromethylstyryl)- isoquinoline Method A) The procedure described in Example 1 , method A) is followed to obtain the title compound as pale yellow solids Yield 92 % M p 180-182 °C (chloroform) Method B) The procedure described in Example 1 , method B) is followed to obtain the title compound Yield 64 % M p 180-182 °C (chloroform) Method C) The procedure described in Example 1 , method C) is followed to obtain the title compound Yield 68 % M p 180-182 °C (chloroform) Analysis for C 20 HnF 6 NO 2 (41 1 30) calculated C 58 40 % H 2 70 %, N 3 41 %, found C 58 22 %, H 2 73 %, N 3 35 % IR (KBr, cm "1 ) 1615, 1478, 1324, 1 104 1 H-NMR (CDCI 3 , 200 MHz) δ 8 72 (1 H, s), 8 04 (1 H, d, J=15 4 Hz), 7 84 (1 H, d, J=15 4 Hz), 7 76 (2H, s), 7 69 (2H, s), 7 66 (1 H, s), 7 43 (1 H, q, J=1 8 Hz), 6 20 (2H, s) 13 C-NMR (CDCI 3 100 6 MHz) δ 155 8, 152 0, 149 0, 139 8 (q, 4 J CF = 1 5 Hz), 136 7, 1 36 2, 131 5, 130 6 (q, 2 J CF =32 8 Hz), 127 7, 125 8 (q, 3 J CF =3 8 Hz), 124 6, 124 6 (q, 1 J CF =273 1 Hz), 124 0 (q, 1 J CF =272 0 Hz), 124 0 102 4, 101 1 , 100 5 (q, 3 J CF =2 7 Hz) MS (m/z, %) 41 1 (37), 410 (100), 392 (10), 382 (13), 382 (2), 380 (2), 353 (1 1 ), 352 (7), 284 (7), 283 (7), 266 (28), 240 (3), 171 (16) 6,7-Methylenedιoxy-4-tπfluoromethyl-1 -(4-tπfluoromethylstyryl)- isoquino nium chloride 1 23 g (3 mmoles) of the above base are reacted with 0 5 cm 3 of 2-propanol containing 3 6 mmoles (25 3 g/100 cm 3 ) of hydrogen chloride Thus 1 03 g (77 %) of hydrochlonde are obtained in the form of light yellow solids M p 259-260 °C (methanol dnsopropyl ether, decomposition) Analysis for C 20 H 12 CIF 6 NO 2 (447 77) calculated C 53 65 %, H 2 70 % Cl 7 92 %, N 3 13 %, found C 53 82 % H 2 63 % Cl 7 87 % N 3 16 % IR (film, cm '1 ) 1630 1482, 1320 1 180, 1 134 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 73 (1 H, s), 8 41 (1 H, s), 8 38 (1 H, d, J=15 4 Hz) 8 16 (2H d J=8 2 Hz) 8 1 1 (1 H, d, J=15 4 Hz), 7 80 (2H, d J=8 2 Hz), 7 34 (1 H, q, J=1 4 Hz), 6 36 (2H, s) Example 6 1 -/2-(4-Trιfluoromethylpheπyl)ethyl/-6,7-ethylenedιoxy- isoquinohne 5.5 g (0.015 moles) of 1 -(4-trifluoromethylstyryl)-6,7- ethylenedioxyisoquinoline are dissolved in 100 cm 3 of methanol. The solution obtained is hydrogenized in the presence of 1 g of palladium/carbon catalyst at a pressure of 15 bar. The catalyst is filtered, and, to the residue, concentrated aqueous ammonia solution is added until a pH value of 9. The precipitated crystalline matter is filtered, and crystallized from ethanol. Thus, 2.4 g (44 %) of the title product are obtained. M.p.: 110-1 1 1 °C. Analysis: for C 20 Hι 6 F 3 NO 2 (359.35) calculated: C 66.85 %, H 4.49 %, N 3.90 %; found: C 66.34 %, H 4.42 %, N 4.03 %. IR (KBr, cm "1 ): 1509, 1292, 1168, 1096, 1065. 1H-NMR (CDCI 3 , 400 MHz) δ: 8.27 (1 H, d, J=5.8 Hz), 7.53 (2H, d, J=8.1 Hz), 7.47 (1 H, s), 7.36 (3H, m), 7.21 (1 H, s), 4^37 ,(4H, m), 3.46 (2H, dd, ^=7.6 Hz, J 2 =8.6 Hz), 3.25 (2H, dd, J=7.6 Hz, J=8.6 Hz). Example 7 1 -/2-(4-Trifluoromethylphenyl)ethyl/-2-methyl-6,7-ethylene- dioxy-1 ,2,3,4-tetrahydroisoquinoline fumarate 2.2 g (0.004 moles) of 1 -/2-(4-trifluoromethylphenyl)ethyl/-2- methyl-6,7-ethylenedioxy-3,4-dihydroisoquinolinium iodide are dissolved in 150 cm 3 of methanol, and, to the solution formed, 1 g of sodium tetrahydroborate are added under stirring. The reaction mixture is stirred at room temperature for 2 hours, then evaporated. To the residue, 100 cm 3 of water are added, the aqueous phase is extracted with dichloromethane, dried over anhydrous sodium sulfate, and evaporated. The residual oily matter is dissolved in ethanol, and an equimolar quantity of fumaric acid dissolved in ethanol are poured to the latter solution. The precipitated crystals are filtered, and recrystalhzed from aqueous acetone. Thus, 1.33 g (67 %) of the title compound are obtained. M.p.: 192-194 °C. Analysis: for C 25 H 26 F 3 N0 2 (493.48) calculated: C 60.85 %, H 5.31 %, N 2.84 %; found: C 60.12 %, H 5.28 %, N 2.82 %. 1 H-NMR (DMSO-d 6 , 400 MHz) δ: 7.60 (2H, d, J=8.1 Hz), 7.39 (2H, d, J=8.1 Hz), 6.64 (1 H, s), 6.61 (2H, s), 6.56 (1 H, s), 4.18 (4H, bs), 3.40 (1 H, t, J=5.2 Hz), 3.06 (1 H, m), 2.80-2.50 (5H, m), 2.39 (3H, s), 2.00 (2H, m). Example 8 1 -/2-(4-Fluorophenyl)ethyl/-2-methyl-6,7-ethylenedioxy-1 ,2,3,4- tetrahydroisoquinoline hydrochlohde 5.0 g (12 mmoles) of 1 -/2-(4-fluorophenyl)ethyl/-2-methyl-6,7- ethylenedioxy-3,4-dihydroisoquinolinium iodide are dissolved in 370 cm 3 of methanol. To the solution formed, 1 g (24 mmoles) of sodium tetrahydridoborate are added under ice cooling, then the reaction mixture is stirred at room temperature for 3 hours, evaporated to the half of the original volume, and 200 cm 3 of water are added. The residual methanol is distilled off, and the aqueous phase is extracted with dichloromethane. The organic solution is dried, and evaporated under reduced pressure. The residue is dissolved in diethyl ether, the pH is adjusted to 1 by the addition of 2-propanol containing hydrogen chloride The precipitated hydrochloπde is filtered, and recrystalhzed from 2- propanol Thus, 3 6 g (82 %) of the title compound are obtained M p 175-177 °C Analysis for C 20 H 23 CIFNO 2 (363 86) calculated C 66 02 %, H 6 37 %, N 3 85 %, found C 65 45 %, H 6 35 %, N 3 95 % 1 H-NMR (DMSO-d 6 , 400 MHz) δ 11 36 (1 H, bs), 7 29 (2H, dd, Jι=5 9 Hz, J 2 =8 2 Hz), 7 10 (2H, t, J=8 8 Hz), 6 76 (1 H, s), 6 74 (1 H, s), 4 30 (1 H, m), 4 23 (4H, m), 3 65-3 15 (2H, m), 2 98 (2H, m), 2 79 (5H, m), 2 44 (1 H, m), 2 05 (1 H, m) Example 9 1-/2-(4-Fluorophenyl)ethyl/-2-methyl-6,7-methylenedιo v y- 1 ,2,3,4-tetrahydroιsoquιnohne hydrochlonde 5 94 g (0 02 moles) of 1 -/2-(4-fluorophenyl)ethyl/-6,7- methylenedιoxy-3,4-dιhydroιsoquιnohne are dissolved in 50 cm 3 of acetone To the solution formed, 14 1 g of methyl iodide are added, and the reaction mixture is allowed to stand at room temperature for 24 hours The precipitated quaternary isoquinolinium salt is filtered, then dissolved in 150 cm 3 of methanol, and 3 5 g of sodium tetrahydridoborate are added in portions at 25-30 °C The reaction mixture is stirred for 2 hours, then evaporated to dryness To the residue, 200 cm 3 of water are added, and the solution is extracted with dichloromethane The organic solution is dried over anhydrous sodium sulfate, and evaporated to dryness The residue is recrystalhzed from ethanol Thus, 3 7 g (52 %) of the title compound are obtained M p 208-211 °C Analysis for Cι 9 H 2 ιCIFN0 2 (349 83) calculated C 65 23 %, H 6 05 %, N 4 00 %, found C 64 80 %, H 6 00 %, N 4 07 % 1 H-NMR (DMSO-d 6 , 400 MHz) δ 11 53 (1 H, bs), 7 31 (2H, dd, Jι=6 0 Hz, J 2 =8 1 Hz), 7 1 (2H, t, J=8 8 Hz), 6 83 (2H, s), 6 2 (2H, s), 4 43 (2H, t, J=5 6 Hz), 3 49 (1 H, m), 3 24 (1 H, m), 2 7- 3 1 (3H, m), 2 78 (3H, s), 2 45 (1 H, m), 2 8 (1 H, m) Example 10 1-/2-(4-Trιfluoromethylphenyl)ethyl/-2-methyl-4-propyl-6,7- ethylenedioxyisoquinohnium iodide 4 0 g (0 01 moles) of 1 -/2-(4-tπfluoromethylphenyl)ethyl/-2- methyl-4-propyl-6,7-ethylenedιoxyιsoquιnohne are dissolved in 100 cm 3 of nitromethane To the solution formed, 14 1 g of methyl iodide are added, and the reaction mixture is boiled for 3 hours The mixture is cooled to room temperature, and the crystalline isoquinohnium salt is filtered The crude product is recrystalhzed from a mixture of acetonitnle and ether Thus, 2 7 g (49 %) of the title compound are obtained M p 214-216 °C Analysis for C 24 H 25 F 3 IN0 2 (543 37) calculated C 53 05 %, H 4 64 %, N 2 58 %, found C 52 83 %, H 4 69 %, N 2 60 % 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 29 (1 H, s), 7 78 (1 H, s), 7 62 (1 H, s), 7 53 (2H, m), 7 42 (2H, m), 4 5 (4H, m), 4 38 (3H, s), 3 87 (2H, t, J=7 8 Hz), 3 26 (2H, t, J=7 8 Hz), 3 4 (2H, t, J=7 8 Hz), 1 8 (2H, m), 1 7 (3H, t, J=7 4 Hz) Example 11 1 -(4-Tπfluoromethylstyryl)-4-propyl-6,7-ethylenedιoxy- isoquinohnium chloride 6 2 g (0 015 moles) of N-/2-(3 4-ethylenedιoxyphenyl)ethyl/-4- tπfluoromethylcinnamamide are dissolved in 90 cm 3 of absolute benzene To the solution formed, 25 cm 3 of phosphor(V) trichloride oxide are added, and the reaction mixture is boiled for 4 hours To the still hot solution, 100 cm 3 of methanol are poured, then evaporated to dryness The addition of methanol and the evaporation are repeated three times using 50 cm 3 of methanol each time Then the methanohc solution of the isoquinohne hydrochlonde is transferred through the acidic ion exchanger Amberlist 46, and the product is precipitated with dnsopropyl ether Thus, 1 3 g (31 %) of the title compound are obtained M p 188-190 °C Analysis for C 23 H 2 ιCIF 3 N0 2 (435 87) calculated C 63 38 %, H 4 86 %, N 3 21 %, found C 63 39 %, H 4 85 %, N 3 19 % 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 48 (1 H, s), 8 22 (1 H, d, J=16 2 Hz), 8 16 (4H, m), 7 86 (2H, d, J=8 3 Hz), 7 71 (1 H, s), 4 56 (2H, m), 4 52 (2H, m), 3 05 (2H, d, t, J=7 6 Hz), 1 7 (2H, hx, J=7.4 Hz), 0.99 (3H, t, J=7.3 Hz). Example 12 1 -/2-(4-Trifluoromethylphenyl)ethyl/-2-methyl-6,7-methylene- dioxy-1 ,2,3,4-tetrahydroisoquinoline 4.89 g (0.01 moles) of 1 -/2-(4-thfluoromethylphenyl)ethyl/-2- methyl-6,7-methylenedioxy-3,4-dihydroisoquιnolinium iodide are dissolved in 80 cm 3 of methanol, and, to the solution formed, 2.1 g of sodium tetrahydridoborate are added in portions. The solution is stirred at room temperature for 3 hours, then evaporated to dryness. To the residue, 150 cm 3 of water are added, and extracted with dichloromethane. The organic phase is dried over anhydrous sodium sulfate, evaporated under reduced pressure, and the residual white solids are recrystalhzed from ethanol. Thus, 2.8 g (77 %) of the title compound are obtained. M.p.: 51 -52 °C. Analysis: for C 20 H 20 F 3 NO 2 (363.3) calculated: C 66.11 %, H 5.55 %, N 3.85 %; found: C 66.08 %, H 5.53 %, N 3.86 %. 1 H-NMR (CDCI 3 , 400 MHz) δ: 7.5 (2H, d, J=8.2 Hz), 7.27 (2H, d, J=8.2 Hz), 6.54 (1 H, s), 6.53 (1 H, s), 5.88 (2H, s), 3.38 (1 H, t, J=5.4 Hz), 3.1 (1 H, m), 2.55-2.84 (5H, m), 2.45 (3H, s), 2.3 (2H, m). Example 13 1 -(4-Thfluoromethylstyryl)-6,7-methylenedioxy-1 ,2,3,4- tetrahydroisoquinoline 3 4 g (0 01 moles) of 1 -(4-tπfluoromethylstyryl)-3,4-dιhydro- isoquinoline are dissolved in 150 cm 3 of methanol To the solution formed, 1 4 g of sodium tetrahydridoborate are added in portions under stirring, and the solution is stirred at room temperature for 3 hours The mixture is evaporated to one fourth of the original volume, and, to the residue, 200 cm 3 of water are added, any methanol present is distilled off, the solid matter is filtered, and washed with water until neutral The product is recrystalhzed from ethanol Thus, 2 6 g (74 %) of the title compound are obtained M p 124-125 °C Analysis for Cι 9 Hι 6 F 3 N0 2 (347 34) calculated C 65 70 %, H 4 64 %, N 4 03 %, found C 65 90 %, H 4 67 %, N 4 06 % 1 H-NMR (CDCI 3 , 200 MHz) δ 7 56 (2H, d, J=8 5 Hz), 7/8 (2H, d, J=8 5 Hz), 6 61 (1 H, d, J=15 8 Hz), 6 6 (1 H, s), 6 58 (1 H, s), 6 4 (1 H, d, J=15 8 Hz), 5 89 (2H, s), 4 58 (1 H, d, J=7 7 Hz), 3 3- 3 0 (2H, m), 2 9-2 6 (2H, m) Example 14 1 -/2-(4-Trιfluoromethylphenyl)ethyl/-2,2-dιmethyl-6,7- methylenedιoxy-1 ,2,3,4-tetrahydroιsoquιnolιnιum iodide 5 1 g (0 01 moles) of 1-/2-(4-tπfluoromethylphenyl)ethyl/-2- methyl-6,7-methylenedιoxy-1 ,2,3,4-tetrahydroιsoquιnolιne are dissolved in 60 cm 3 of acetone To the solution formed, 8 cm 3 of methyl iodide are added, and the reaction mixture is stirred at room temperature for 24 hours The precipitated matter is filtered, and recrystalhzed from ethanol Thus, 4 2 g (83 %) of the title product are obtained M p 229-231 °C Analysis for C 2 ιH 23 F 3 IN0 2 (505 32) calculated C 49 92 %, H 4 59 %, N 2 77 %, found C 49 01 %, H 4 61 %, N 2 73 % 1 H-NMR (DMSO-de, 400 MHz) δ 7 66 (2H, d, J=8 8 Hz), 7 44 (2H, d, J=8 8 Hz), 6 89 (1 H, s), 6 82 (1 H, s), 6 06 (2H, s), 4 55 (1 H, m), 3 77 (2H, m), 3 62 (2H, m), 3 33 (2H, s), 3 29 (3H, s), 3 09-3 05 (2H, m), 2 88-2 86 (1 H, m), 2 69-2 68 (1 H, m) Example 15 1-(4-Trιfluoromethylstyryl)-2,2-dιmethyl-6,7-methylenedιoxy- 1 ,2,3,4-tetrahydroιsoquιnohnιum iodide The procedure described in Example 14 is followed to btaιn the title compound Yield 59 % M p 256-258 °C Analysis for C 2 ιH 2 ιFIN0 2 (503 30) calculated C 50 31 %, H 4 21 %, N 2 78 %, found C 49 88 %, H 4 25 %, N 2 87 % Example 16 1 -/2-(4-Fluorophenyl)ethyl/-2,2-dιmethyl-6,7-methylenedιoxy- 1 ,2,3,4-tetrahydroιsoquιnohnιum iodide 2 93 g (6 5 mmoles) of 1 -/2-(4-fluorophenyl)ethyl/-2,2-dιmethyl- 6,7-methylenedιoxy-1 ,2,3,4-tetrahydroιsoquιnohne and 2 8 cm 3 of methyl iodide are boiled in 40 cm 3 of nitromethane under stirring for 3 hours The mixture is cooled to room temperature, then allowed to stand in a refrigerator. The crystalline matter is filtered, washed with cold acetone, and recrystalhzed from ethanol. Thus, 1.3 g (43 %) of the title compound are obtained. M.p.: 213-215 °C. Analysis: for C 20 H 23 FINO 2 (455.31) calculated: C 52.76 %, H 5.09 %, N 3.08 %; found: C 53.1 1 %, H 5.21 %, N 3.15 %. 1 H-NMR (CDCI 3 , 400 MHz) δ: 7.28 (2H, m), 6.99 (2H, m), 6.78 (1 H, s), 6.7 (1 H, s), 6.02 (2H, s), 4.85 (1 H, m), 3.83 (2H, m), 3.45 (3H, s), 3.21 (3H, s), 3.15-3.1 (2H, m), 2.86-2.61 (2H, m), 2.52-2.0 (2H, m). Example 17 1 -/2-(4-Fluorophenyl)ethyl/-2-methyl-6,7-methylenedioxy- isoquinolinium iodide A solution of 5.9 g (0.02 moles) of 1 -/2-(4-fluorophenyl)ethyl/-2- methyl-6,7-methylenedioxy-isoquinoline and 6.1 cm 3 of methyl iodide in 250 cm 3 of acetone is allowed to stand at room temperature for 20 hours. The suspension obtained is cooled to 0 °C, filtered, washed with cold acetone, and the product is recrystalhzed from methanol. Thus, 4.7 g (54 %) of the title compound are obtained. M.p.: 224-227 °C. Analysis: for Cι 9 Hι 7 FIN0 2 (437.25) calculated: C 52.19 %, H 3.92 %, N 3.20 %; found: C 52.24 %, H 3.99 %, N 3.29 %. IR (KBr, cm "1 ): 1031 , 932. 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 58 (1 H, d, J=6 8 Hz), 8 19 (1 H, d, J=6 8 Hz), 8 05 (1 H, s), 7 71 (1 H, s), 7 41 (2H, dd, Jι=8 5 Hz, J 2 =5 7 Hz), 7 14 (2H, t, J=8 5 Hz), 6 46 (2H, s), 4 38 (3H, s), 3 78 (2H, t, J=8 1 Hz), 3 04 (2H, t, J=8 1 Hz) Example 18 1 -/2-(4-Fluorophenyl)ethyl/-2,3-dιmethyl-6,7-methylenedιoxy- isoquinohnium iodide 3 0 g (0 0097 moles) of 1 -/2-(4-fluorophenyl)ethyl/-2,3-dιmethyl- 6,7-methylenedιoxyιsoquιnohne and 3 2 cm 3 of methyl iodide are dissolved in 25 cm 3 of nitromethane The reaction mixture is boiled for 1 5 hours, then 1 6 cm 3 of methyl iodide are added, and the reaction mixture is boiled for further 1 hour The mixture is cooled to room temperature, 50 cm 3 of diethyl ether are poured to it, stirred for 2 hours, then filtered The product is recrystalhzed from dimethylformamide Thus, 2 19 g (50 %) of the title compound are obtained M p 271 -273 °C Analysis for C 20 Hι 9 FINO 2 (451 28) calculated C 53 23 %, H 4 24 %, N 3 10 %, found C 53 28 %, H 4 12 %, N 3 14 % 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 09 (1 H, s), 7 92 (1 H, s), 7 53 (1 H, s), 7 40 (2H, m), 7 13 (2H, m), 6 40 (2H, s), 4 22 (3H, s), 3 83 (2H, t, J=8 0 Hz), 3 00 (2H, t, J=8 0 Hz), 2 80 (3H, s) Example 19 1 -(4-Fluorostyryl)-6,7-methylenedioxy-1 ,2,3,4-tetrahydroisoquinoline To a solution of 4.4 g (0.015 moles) of 1-(4-fluorostyryl)-6,7- methylenedioxy-3,4-dihydroisoquinoline in 200 cm 3 of methanol, 1.6 g of sodium tetrahydridoborate are added in three portions under stirring. The reaction mixture is stirred at 25 to 30 °C for 2 hours (TLC benzene: methanol 8:2, R f =0.46 UV), then evaporated to dryness under reduced pressure. To the residue, 150 cm 3 of water are added, and the mixture is extracted three times with dichloromethane. The combined organic phases are dried over anhydrous sodium sulfate, evaporated, the residue is crystallized from diethyl ether. The product is filtered, and recrystalhzed from ethanol. Thus, 2.7 g (82 %) of the title compound are obtained. M.p.: 112-113 °C. Analysis: for Cι 8 H 16 FN0 2 (217.33) calculated: C 72.71 %, H 5.42 %, N 4.71 %; found: C 72.37 %, H 5.41 %, N 4.51 %. 1 H-NMR (CDCIs, 200 MHz) δ: 7.32 (2H, m), 6.96 (2H, m), 6.93 (1 H, s), 6.55 (1 H, s), 6.53 (1 H, s), 6.47 (1 H, d, J=15.8 Hz), 6.18 (1 H, dd, Jι = 15.8 Hz, J 2 =8.0 Hz), 5.8 (2H, s), 4.51 -4.48 (1 H, m), 3.24-3.17 (1 H, m), 3 02-2.99 (1 H, m), 2.99-2.68 (2H, m). Example 20 1 -/2-(4-Trifluoromethylphenyl)ethyl/-2-methyl-6,7-methylene- dioxyisoquinolinium iodide 5 1 g (0 015 moles) of 1-/2-(4-tπfluoromethylphenyl)ethyl/-2- methyl-6,7-methylenedιoxyιsoquιnohne and 5 cm 3 of methyl iodide are boiled in 25 cm 3 of nitromethane for 30 minutes, the mixture is cooled to room temperature, poured into 250 cm 3 of acetone, and stirred The precipitated crystalline solids are filtered, washed with cold acetone, and the crude isoquinohnium salt is recrystalhzed from a mixture of hexane and ethanol in a ratio of 4 1 Thus, 5 4 g (75 %) of the title compound are obtained M p 258-260 °C Analysis for C 20 Hι 7 F 3 INO 2 (487 26) calculated C 49 30 %, H 3 52 %, N 2 87 %, found C 48 62 %, H 3 44 %, N 2 93 % 1 H-NMR (DMSO-d 6 , 200 MHz) δ 8 61 (2H, d, J=6 8 Hz), 8 20 (2H, d, J=6 8 Hz), 8 05 (2H, s), 7 71 -7 61 (2H, m), 6 44 (2H, s), 4 43 (3H, s), 3 83 (2H, t, J=8 0 Hz), 3 14 (2H, t, J=8 0 Hz) Example 21 1-(4-Trιfluoromethylstyryl)-2-methyl-6,7-methylenedιoxy- isoquinolinium iodide 6 8 g (0 02 moles) of 1-(4-trιfluoromethylstyryl)-2-methyl-6,7- methylenedioxyisoquinohπe are dissolved in 40 cm 3 of dichloromethane, and, to the solution formed, 9 95 g (0 065 moles) of methyl iodide are added The reaction mixture is boiled for 1 5 hours, then evaporated to dryness, the residue is stirred with diethyl ether, cooled to 5 °C, filtered, washed with cold ether, and recrystalhzed from methanol Thus, 5 9 g (61 %) of the title compound are obtained M p 233-235 °C Analysis for C 20 Hι 5 F 3 INO 2 (485 25) calculated C 49 51 %, H 3 12 %, N 2 89 %, found C 49 05 %, H 3 18 %, N 2 82 % 1 H-NMR (CDCI 3 , 400 MHz) δ 8 77 (1 H, d, J=11 Hz), 8 12 (1 H, d, J=11 0 Hz), 7 80 (3H, m), 7 63 (2H, d, J=13 2 Hz), 7 58 (1 H, s), 7 44 (1 H, s), 7 31 (1 H, m), 6 29 (2H, s), 4 62 (3H, s) Example 22 1 -(4-Trιfluoromethylstyryl)-2-methyl-6,7-methylenedιoxy- 1 ,2,3,4-tetrahydroisoquinoline 5 6 g (0 012 moles) of 1 -(4-trιfluoromethylstyryl)-2-methyl-6,7- methylenedioxyisoquinohnium iodide are dissolved in 110 cm 3 of methanol, and, to the solution formed, 0 8 g of sodium tetrahydridoborate are added in two portions The solu^'on is stirred for 1 hour, then evaporated under reduced pressure To the residue, 100 cm 3 of water are added, and the mixture is extracted three times using 50 cm 3 of dichloromethane each time The organic phase is dried over anhydrous sodium sulfate, and evaporated to dryness The residue is recrystalhzed from ethanol Thus, 2 5 g (57 %) of the title compound are obtained M p 85-88 °C Analysis for C 20 Hι 8 F 3 NO 2 (361 37) calculated C 66 48 %, H 5 02 %, N 3 88 %, found C 66 60 %, H 5 13 %, N 3 91 % IR (KBr, cm 1 ) 2844, 1166, 1 121 , 957 1H-NMR (DMSO-d 6 , 400 MHz) δ 7 69 (4H, m), 6 78 (1 H, d, J=8 7 Hz), 6 69 (1 H, s), 6 56 (1 H, s), 6 34 (1 H, d, J=8 7 Hz), 5 93 (2H, m), 3 86 (1 H, m), 3 29 (3H, s), 3 1 -2 9 (4H, m) Example 23 1-(4-Fluorostyryl)-2-methyl-6,7-methylenedιoxyιsoquιnolιnιum iodide 38 1 g (0 13 moles) of 1 -(4-fluorostyryl)-2-methyl-6,7- methylenedioxyisoquinohne are dissolved in 200 cm 3 of nitromethane To the solution formed, 98 4 g of methyl iodide are added The reaction mixture is stirred at 120 °C for 1 5 hours The precipitated crystalline solids are filtered to obtain 50 9 g of crude product 12 g of the crude product are recrystalhzed from 70 ml of methanol Thus, 7 4 g (62 of the title compound are obtained M p 228-230 °C Analysis for d 9 Hι 5 FIN0 2 (435 25) calculated C 52 43 %, H 3 47 %, N 3 22 %, found C 52 05 %, H 3 38 %, N 3 25 % 1 H-NMR (DMSO-d 6 , 200 MHz) δ 8 62 (1 H, d, J=6 0 Hz), 8 21 (1 H, d, J=6 0 Hz), 7 93 (2H, m), 7 80 (1 H, s), 7 75 (1 H, m), 7 62 (1 H, d, J=12 4 Hz), 7 38-7 32 (3H, m), 6 44 (2H, s), 4 34 (3H, s) Example 24 1 -(4-Fluorostyryl)-2-methyl-6,7-methylenedιoxy-1 ,2,3,4-tetra- hydroisoquinolinium chloride 30 g (0 07 moles) of 1 -(4-fluorostyryl)-2-methyl-6,7- methylenedιoxy-1 ,2,3,4-tetrahydroιsoquιnolιnιum iodide are dissolved in 1200 cm 3 of methanol, and, to the solution formed, 4.7 g of sodium tetrahydridoborate are added in portions at 20 °C. The solution is stirred at room temperature for 1 hour, then evaporated under reduced pressure. To the residue, 500 cm 3 of water are added. The aqueous solution is extracted with altogether 440 cm 3 of dichloromethane. The organic phase is dried over anhydrous sodium sulfate. After the addition of 20 cm 3 of ethanol containing hydrogen chloride, the solution is evaporated to dryness, the residue is crystallized from benzene to obtain 18.7 g of crude product which is recrystalhzed from 110 cm 3 of 2-propanol. Thus, 16.3 g (76 %) of the title compound are obtained. M.p.: 210-213 °C. Analysis: for Cι 9 Hι 9 CIFN0 2 (347.33) calculated: C 65.61 %, H 5.51 %, N 4.03 %, found: C 65.68 %, H 5.59 %, N 3.98 %. 1 H-NMR (CDCI 3 , 200 MHz) δ: 12.1 (1 H, bs), 7.36 (2H, m), 6.98 (2H, m), 6.59-6.52 (3H, m), 6.02 (1 H, m), 5.85 (2x1 H, 2xs), 3.78-3.75 (1 H, m), 3.01 -2.4 (4H, m), 3.45 (3H, s). Example 25 1 -(4-Thfluoromethylstyryl)-2-ethyl-6,7-methylenedioxy- isoquinolinium iodide 2.0 g (5.8 mmoles) of 1 -(4-trifluoromethylstyryl)-2-ethyl-6,7- methylenedioxyisoquinoline are dissolved in 15 cm 3 of nitromethane, and, to the solution formed, 4.7 cm 3 of ethyl iodide are added. The solution is stirred at 120 °C for 4 hours, then evaporated under reduced pressure. The residue is crystallized from diethyl ether, the crude product is recrystalhzed from acetone Thus, 1 9 g (65 %) of the title compound are obtained M p 234-236 °C Analysis for C 2 ιHι 7 F 3 IN0 2 (499 27) calculated C 50 52 %, H 3 43 %, N 2 81 %, found C 50 34 %, H 3 40 %, N 2 81 % IR (KBr, cm 1 ) 1439, 1462, 1328 H-NMR (DMSO-d 6 , 400 MHz) δ 8 68 (1 H, d, J=6 9 Hz), 8 28 (1 H, d, J=6 9 Hz), 8 06 (2H, d, J=8 2 Hz), 7 89 (2H, d, J=8 2 Hz), 7 86 (1 H, d, J=16 7 Hz), 7 8 (1 H, s), 7 76 (11-1, s), 7 40 (11-1, d, J=16 7 Hz), 6 44 (2H, s), 4 70 (2H, q, J=7 2 Hz), 1 49 (3H, t, J=7 2 Hz) Example 26 1 -(4-Cyaπostyryl-2-methyl-6,7,8-trιmethoxyιsoquιnohn" 'm iodide 1 8 g (55 mmoles) of 1-(4-cyanostyryl-2-methyl-6,7,8- tnmethoxyisoquinohne are dissolved in 15 cm 3 of nitromethane To the solution obtained, 3 7 g of methyl iodide are added, and the reaction mixture is stirred at 120 °C for 4 hours The mixture is evaporated, the residue is crystallized from diethyl ether The crystals are dissolved in 40 cm 3 of dichloromethane, and the product is precipitated by the addition of 10 ml of cyclohexane Thus, 1 g (40 %) of the title compound are obtained M p 130-133 °C Analysis for C 23 H 23 IN 2 0 3 (502 35) calculated N 5 58 %, found N 5 38 % IR (KBr, cm 1 ) 3438, 2225, 1406 1 H-NMR (DMSO-d 6 , 200 MHz) δ 8 15 (1 H, s), 8 02 (1 H, d, J=16 9 Hz), 7 91 (4H, m), 7 45 (1 H, s), 6 95 (1 H, d, J=16 8 Hz), 4 14 (3H, s), 4 06 (3H, s), 3 85 (3H, s), 3 68 (3H, s), 2 80 (3H, s) Example 27 1-/2-(3,4-Dιmethoxyphenyl)ethyl/-2-methyl-6,7-dιmethoxy- isoquinohnium iodide 7 2 g (0 02 moles) 1 -(2-(3,4-dιmethoxyphenyl)ethyl/-6,7- dimethoxyisoquiπoline are dissolved in 60 cm 3 of nitromethane To the solution formed, 14 2 g of methyl iodide are added, and the reaction mixture is stirred at 120 °C for 4 hours Then the mixture is cooled, and 100 cm 3 of diethyl ether are added to precipitate the product in crystalline form The crystals are filtered to obtain 8 7 g of crude product 5 7 g of the crude product are recrystalhzed from a mixture of water and ethanol Thus, 4 8 g (71 %) of the title compound are obtained M p 188-190 °C Analysis for C 22 H 28 IN0 5 (513 37) calculated N 2 73 %, found N 2 63 % Example 28 1-/2-(3,4-Dιmethoxyphenyl)ethyl/-6,7-dιmethoxyιsoquιnohne 3 51 g (0 01 moles) of 1 -(3,4-dιmethoxystyryl)-6,7-dιmethoxy- isoquinohne are dissolved in 100 cm 3 of acetic acid To the solution formed, 0 5 g of Pd/C catalyst are added, and the mixture is hydrogenized at room temperature and 10 bar pressure until the end of hydrogen gas consumption The catalyst is removed by filtration, the filtrate is evaporated under reduced pressure The residue is dissolved in 50 cm 3 of methanol, and, by the addition of about 50 g of crushed ice and 10 cm 3 of 25 % aqueous ammonia, the base is prepared The precipitated crystalline product is filtered, and washed with cold water Thus, 1 5 g (43 %) of the title compound are obtained M p 146-147 °C Analysis for C 2 ιH 23 N0 4 (353 422) calculated C 71 37 %, H 6 56 %, N 3 96 %, found C 71 04 %, H 6 54 %, N 3 89 % IR (KBr, cm "1 ) 1516, 1234, 1158 1 H-NMR (CDCIs, 400 MHz) δ 8 35 (1 H, d, J=5 5 Hz), 7 39 (1 H, d, J=5 5 Hz), 7 22 (1 H, s), 7 05 (1 H, s), 6 81 (2H, s), 6 74 (1 H, s), 4 01 (3H, s), 3 96 (3H, s), 3 85 (3H, s), 3 80 (3H, s), 3 48 (2H, t, J=7 8 Hz), 3 15 (2H, t, J=7 8 Hz) Example 29 1 -/2-(3,4-Dιmethoxyphenyl)ethyl/-2-methyl-6,7-dιmethoxy- 1 ,2,3,4-tetrahydroιsoquιnolιne fumarate To a solution of 3 0 g (0 006 moles) of 1 -/2-(3,4-dιmethoxy- phenyl)ethyl/-2-methyl-6,7-dιmethoxy-1 ,2,3,4-tetrahydro- isoquinohnium iodide in 200 cm 3 of methanol, 0 45 g of sodium tetrahydridoborate are added at room temperature under stirring The reaction mixture is stirred for 2 hours, then evaporated under reduced pressure To the residue, 200 cm 3 of water are added, the aqueous solution is extracted three times using 60 cm 3 of dichloromethane each time The combined organic phases are dried over anhydrous sodium sulfate, and evaporated under reduced pressure to yield 2 g of crude product which are dissolved in 20 cm 3 of ethanol To the solution formed, a solution of 0 62 g of fumanc acid in 40 cm 3 of ethanol is poured The precipitated crystalline fumarate salt is filtered, washed with some cold ethanol Thus, 1 1 g (34 %) of the title compound are obtained M p 84-85 °C IR (KBr, cm "1 ) 3430, 2540, 1713, 1518, 1257 1H-NMR (DMSO-d 6 , 400 MHz) δ 6 83 (1 H, d, J=8 2 Hz), 6.76 (1 H, d, J=1 5 Hz), 6 69 (1 H, dd, J, = 1 6 Hz, J 2 =8 1 Hz), 6 67 (1 H, s), 6 65 (1 H, s), 6,60 (2H, s), 3 72 (3H, s), 3 70 (3H, s), 3 70 (3H, s), 3 49 (1 H, m), 3 15 (1 H, m), 2 70 (2H, m), 2 60 (2H, m), 2 45 (3H, s), 2 44 (1 H, m), 2 00 (2H, m) Example 30 1-/2-(4-Trιfluoromethylphenyl)ethyl/-4-propyl-6,7-ethylenedιoxy- isoquinohne 4 8 g (0-012 moles) 1 -(4-trιfluoromethylstyryl)-4-propyl-6,7- ethylenedioxyisoquinohne are dissolved in 200 cm 3 of acetic acid, and the solution is hydrogenized in the presence of 1 g of Pd/C catalyst at room temperature and 10 bar pressure until the end of the hydrogen gas consumption. The catalyst is filtered, the filtrate is evaporated to dryness, the residue is dissolved in aqueous methanol, and concentrated aqueous ammonia is added to prepare the free base. Thus, 3.9 g (81 %) of the title compound are obtained. M.p.: 89-90 °C. Analysis: for C 23 H 22 F 3 N0 2 (401.432) calculated: C 68.82 %, H 5.52 %, N 3.49 %; found: C 68.19 %, H 5.51 %, N 3.46 %. IR (KBr, cm "1 ): 1512, 1331 , 1109, 1069. 1H-NMR (CDCIs, 200 MHz) δ: 8.1 1 (1 H, s), 7.54 (2H, d, J=8.4 Hz), 7.50 (1 H, s), 7.41 (1 H, s), 7.39 (2H, d, J=6.0 Hz), 4.40 (4H, m), 3.50 (2H, m), 3.25 (2H, m), 2.88 (2H, t, J=7.7 Hz), 1.75 (2H, hx, J=7.6 Hz), 1.02 (3H, t, J=7.3 Hz). Example 31 1-(4-Trifluoromethylstyryl)-4-propyl-6,7-ethylenedioxy- isoquinolinium chloride 0.9 g (3.7 mmoles) of 1 -methyl-6,7-ethylenedioxyisoquinoline, 0.7 g (4.1 mmoles) of 4-thfluoromethylbenzaldehyde and 3 cm 3 of acetic anhydride are stirred at 150 to 160 °C for 3 hours, then the mixture is evaporated under reduced pressure. The 1.3 g of crude product obtained are dissolved in 25 cm 3 of acetone. To the solution formed, 2-propanol containing hydrogen chloride is added, the precipitated hydrochlonde salt is filtered, washed with some cold acetone. Thus, 0.6 g (37 %) of the title compound are obtained. M.p.: 203-210 °C. Analysis: for C 23 H 2 ιCIF 3 N0 2 (435.87) calculated C 63 38 %, H 4 86 %, N 3 21 %, found C 63 39 %, H 4 85 %, N 3 19 % IR (KBr, cm "1 ) 3420, 2526, 1326, 1067 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 48 (1 H, s), 8 32 (1 H, d, J=16 2 Hz), 8 16 (4H, m), 7 86 (2H, d, J=8 3 Hz), 7 71 (1 H, s), 4 56 (2H, m), 4 52 (2H, m), 3 05 (2H, d, t, J=7 6 Hz), 1 70 (2H, hx, J=7 4 Hz), 0 99 (3H, t, J=7 3 Hz) Example 32 1 -(3,4-Dιmethoxystyryl)-6,7-ethylenedιoxyιsoquιnohne 5 9 g (29 mmoles) of 1 -methyl-6,7-ethylenedιoxyιsoquιnohne and 5 2 g (31 mmoles) of 3,4-dιmethoxybenzaldehyde are stirred in 4 cm 3 of acetic anhydride at 160 °C for 3 hours The reaction mixture is evaporated under reduced pressure,, and the residual oil is purified by column chromatography The crude product obtained is recrystalhzed twice from 2-propanol Thus, 5 1 g (50 %) of the title compound are obtained M p 141 -143 °C Analysis for C 21 H 19 N0 4 (349 39) calculated C 72 19 %, H 5 48 %, N 4 01 %, found C 71 56 %, H 5 60 %, N 3 98 % IR (KBr, cm 1 ) 3420, 1505, 1271 , 1 137 1 H-NMR (CDCI3, 200 MHz) δ 8 35 (1 H, d, J=5 39 Hz), 7 94 (1 H, d, J=15 8 Hz), 7 79 (1 H, s), 7 67 (1 H, d, J=15 8 Hz), 7 37 (1 H, d, J=5 5 Hz), 7 28 (1 H, m), 7 23 (2H, m), 6 91 (1 H, d, J=8 1 Hz), 4 40 (4H, s), 3 98 (3H, s), 3 93 (3H, s) Example 33 1 -(4-Trιfluoromethylstyryl)-4-propyl-6,7-methylenedιoxy- isoquinohne 3 5 g (15 mmoles) of 1 -methyl-4-propyl-6,7-methylenedιoxy- isoquinohne and 4 0 g (22 6 mmoles) of 4-trιfluoromethyl- benzaldehyde are stirred in 35 cm 3 of acetic anhydride at 160 °C for 4 hours The reaction mixture is evaporated under reduced pressure, and the residue is crystallized from diethyl ether The 2 17 g of crude product obtained are recrystalhzed from 40 cm 3 of absolute ethanol Thus, 1 6 g (28 %) of the title compound are obtained M p 156-158 °C Analysis for C 22 Hι 8 F 3 N0 2 (385 389) calculated C 68 57 %, H 4 71 %, N 3 63 %, found C 68 43 % H 4 76 %, N 3 55 % IR (KBr, cm 1 ) 1470, 1328, 1234, 1 120 1 H-NMR (CDCI 3 , 400 MHz) δ 8 28 (1 H, s), 7 93 (1 H, d, J=15 6 Hz), 7 83 (1 H, d, J=15 6 Hz), 7 74 (2H, d, J=8 2 Hz), 7 63 (2H, d, J=8 1 Hz), 7 60 (1 H, s), 7 26 (1 H, s), 6 13 (2H, s), 2 90 (2H, t, J=7 6 Hz), 1 75 (2H, hx, J=7 5 Hz), 1 03 (3H, t, J=7 4 Hz) Example 34 1 -(4-Fluorostyryl)-6,7-methylenedιoxy-3,4-dιhydro- isoquinohnium chloride 12 5 g (0 04 moles) of N-/2-(3,4-methylenedιoxyphenyl)-ethyl/- 4-fluorocinnamamide are dissolved in 100 cm 3 of benzene, and, to the solution formed, 25 ml of phosphor(V) trichloride oxide are poured. The mixture is boiled for 1.5 hours, then cooled to 10 °C, and stirred at the latter temperature for 1 hour. The crystalline crude product is filtered, washed with a low amount of benzene at 10 °C, and recrystalhzed from 400 cm 3 of 2- propanol. Thus, 7.1 g (53.7 %) of the title compound are obtained. M.p.: 219-221 °C. Example 35 1 -(4-Thfluoromethylstyryl)-6,7-methylenedioxy-3,4-dihydro- isoquinolinium chloride 20 g (0.055 moles) of 2-(3,4-methylenedioxyphenyl)ethyl-N-4- thfluoromethylcinnamamide are boiled in 70 cm 3 of benzene in the presence of 20 cm 3 of phosphor(V) trichloride oxide for 3.5 hours. The reaction mixture is cooled to 20 °C, the precipitated salt is washed with some hexane, and recrystalhzed from 110 cm 3 of ethanol. Thus, 7.2 g (72 %) of the title compound are obtained. M.p.: 208-212 °C. Analysis: for Cι 9 Hι 5 CIF 3 N0 2 (381.70) calculated: C 59.78 %, H 3.96 %, Cl 9.29 %, N 3.67 %; found: C 59.78 %, H 3.94 %, Cl 9.32 %, N 3.61 %. Example 36 A) 4,6-Dimethoxy-1 -styryl-4-trifluoromethyl-3,4-dihydro- isoquinolinium maleate 3.79 g (10 mmoles) of N-cinnamoyl-3,3,3-trifluoro-2-methoxy-2- (3-methoxyphenyl)propylamine are stirred in 4.46 cm 3 (7.67 g, 50 mmoles) of phosphor(V) trichloride oxide at 85 °C for 16 hours. The reaction mixture cooled to room temperature is poured onto 40 cm 3 of ice water. The pH is adjusted to 11 by the addition of concentrated aqueous ammonia. The solution is extracted three times using 30 cm 3 of ethyl acetate each time, the combined organic phases are dried over anhydrous magnesium sulfate, and evaporated. The crude base is dissolved in 10 cm 3 of methanol, and, to the solution formed, a solution of 1.16 g (10 mmoles) of maleic acid in 10 cm 3 of methanol, then 40 cm 3 of diisopropyl ether are added, drop by drop. The precipitated crystals are filtered, washed with 10 cm 3 of diisopropyl ether. Thus, 2.54 g (53 %) of the title compound are obtained. M.p.: 149-151 °C (ethanol-diisopropyl ether). Analysis: for C 24 Hι 2 F 3 N0 6 (477.44) calculated: C 60.38 %, H 4.64 %, N 2.93 %; found: C 60.50 %, H 4.56 %, N 3.03 %. IR (film, cm "1 ): 1600, 1493, 1252, 1177. 1H-NMR (DMSO-d 6 , 400 MHz) δ: 8.14 (1 H, d, J=8.8 Hz), 7.86 (2H, dd, J=8.7 Hz, J=5.7 Hz), 7.57 (1 H, d, J=15.8 Hz), 7.50- 7.40 (3H, m), 7.13 (1 H, d, J=3.0 Hz), 6.21 (2H, s), 4.24 (2H, s), 3.92 (3H, s), 3.30 (3H, s). B) 4,6-Dimethoxy-1 -styryl-4-trifluoromethyl-3,4-dihydro- isoquinolinium chloride 3.61 g (10 mmoles) of the crude base are dissolved in 40 cm 3 of diisopropyl ether, and, to the solution formed, 1 73 cm 3 of 2- propanol containing 12 moles (25 3 g/100 cm 3 ) of hydrogen chloride are added, drop by drop The precipitated crystals are filtered, washed with 10 cm 3 of diisopropyl ether Thus, 2 11 g (53 %) of the title compound are obtained M p 188 °C (ethanol) Analysis for C 20 Hι 9 CIF 3 NO 2 (397 82) calculated C 60 38 %, H 4 81 %, Cl 8 91 %, N 3 54 %, found C 60 24 %, H 4 84 %, Cl 8 92 %, N 3 49 % IR (film, cm 1 ) 3435, 1508, 1477 1 H-NMR (DMSO-d 6 + CDCI 3 , 400 MHz) δ 8 49 (1 H, d, J=8 9 Hz), 8 22 (1 H, m), 7 88 (2H, dd, J=7 6 Hz, J=1 8 Hz), 7 73 (1 H, d, J=16 1 Hz), 7 53 (3H, m), 7 35 (1 H, dd, J=8 9 Hz, J=2 6 Hz), 7 29 (1 H, d, J=2 6 Hz), 6 60 (1 H, bs), 4 42 (1 H, d, J=16 0 Hz), 4 26 (1 H, d, J=16 0 Hz), 4 04 (3H, s), 3 42 (3H, s) 13 C-NMR (DMSO-d 6 + CDCI 3 , 100 6 Mhz) 166 9, 166 6, 149 6, 135 7, 134 2, 133 7, 132 3, 129 8, 129 3, 124 4 (q, 1 J CF =287 5 Hz), 119 0, 115 9, 115 8, 114 7, 75 0 ( 2 J CF =28 5 Hz), 55 8, 53 3, 42 2 Example 37 1 -/2-(4-Fluorophenyl)ethyl/-2-methyl-6,7-ethylenedιoxy-3,4- dihydroisoquinohnium bromide 2 33 g (0 0075 moles) of 1 -/2-(4-fluoropheπyl)ethyl/-2-methyl- 6,7-ethylenedιoxy-1 ,2,3,4-tetrahydroιsoquιnolιne are dissolved in 100 cm 3 of dichloromethane The solution is cooled to 0-5 °C, and 1 6 g (0 009 moles) of N-bromosuccinimide are added in several portions during 15 minutes. The mixture is stirred at the latter temperature for 1 hour, then at room temperature for 2 hours. The precipitated crystals are filtered, the filtrate is evaporated, and the residual solids are recrystalhzed from acetone. Thus, 1.76 g (58 %) of the title compound are obtained. M.p.: 177-180 °C. Analysis: for C 20 H 2 ιBrFNO 2 (406.30) calculated: H 5.21 %, N 3.45 %; found: H 5.43 %, N 3.29 %. IR (KBr, cm "1 ): 1735, 1301 , 1219. 1 H-NMR (DMSO-d 6 , 200 MHz) δ: 7.61 (s, 1 H), 7.31 (m, 2H), 7.11 (m, 2H), 6.99 (s, 1 H), 4.35 (m, 4H), 3.95 (m, 2H), 3.66 (s, 3H), 3.47 (m, 2H), 2.94 (m, 4H). Example 38 1-/2-(4-Trifluoromethylphenyl)ethyl/-2-methyl-6,7-ethylene- dioxy-3,4-dihydroisoquinolinium iodide 2.8 g (0.0075 moles) of 1 -/2-(4-thfluoromethylphenyl)ethyl/-2- methyl-6,7-ethylene-dioxy-3,4-dihydroisoquinoline are dissolved in 120 cm 3 of acetone. To the solution formed, 5 cm 3 of methyl iodide are added. The mixture is boiled for 1 hour, then cooled to 0-5 °C with ice water, and stirred at this temperature for 2-3 hours. After crystallization, the crystals are filtered, washed with cold acetone, and recrystallized from acetone. Thus, 2.2 g (58 %) of the title compound are obtained. M.p.: 205-207 °C. Analysis: for C 2 ιH 2 ιF 3 IN0 2 (503.30) calculated C 50 12 %, H 4 21 %, N 2 78 %, found C 49 10 %, H 4 11 %, N 2 71 % 1 H-NMR (CDCI 3 , 400 MHz) δ 7 56 (2H, d, J=8 2 Hz), 7 37 (2H, d, J=8 2 Hz), 7 18 (1 H, s), 6 78 (1 H, s), 4 36 (2H, m), 4 27 (2H, m), 4 12 (2H, t, J=7 6 Hz), 3 90 (3H, s), 3 53 (2H, t, J=7 6 Hz), 3 18 (4H, m) Example 39 6,7-Ethylenedιoxy-1 -/2-(4-trιfluoromethylphenyl)ethyl/-3,4- dihydroisoquino ne 14 2 g (0 037 moles) of 2-(3,4-ethylenedιoxyphenyl)-ethyl-N-3- (4-trιfluoromethylphenyl)propιonyl amide are dissolved in 80 cm 3 of toluene To the solution obtained, 12 cm 3 of phosphor(V) trichloride oxide are added, drop by drop, the reaction mixture is heated to 80 °C and stirred at this temperature for 2 5 hours The precipitated crystalline dihydroisoquinohne is filtered and recrystalhzed from ethanol The product obtained (12 g) is dissolved in 90 cm 3 of methanol, made alkaline to pH 9 by the addition of 20 % aqueous sodium hydroxide solution, the precipitated matter is filtered, washed with aqueous methanol (5 1), and recrystalhzed from a mixture of ethanol and water Thus, 1 44 g (41 %) of the title compound are obtained M p 85 °C Analysis for C 20 Hι 8 NO 2 (361 37) calculated C 66 48 %, H 5 02 %, N 3 88 %, found C 66 34 %, H 5 04 %, N 3 90 % 1 H-NMR (DMSO-de, 400 MHz) δ 7 61 (2H, d, J=8 0 Hz), 7 47 (2H, d, J=8 0 Hz), 7 10 (1 H, s), 6 74 (1 H, s), 4 24 (4H, m), 3 48 (2H, t, J=7 4 Hz), 2 96 (4H, m), 2 47 (2H, t, J=7 1 Hz) Example 40 7-Chloro-1-/2-(4-trιfluoromethylphenyl)ethyl/-3,4-dιhydro- isoquinohne hydrochlonde 10 0 g (0 028 moles) of N-/2-(4-chlorophenyl)ethyl/-3-(4- trιfluoromethylphenyl)propιonyl amide are dissolved in 80 cm 3 of xylene To the stirred mixture, 12 g of phosphor(V) oxide are added, and the reaction mixture is stirred at 110 to 120 °C for 5 hours The mixture is cooled to room temperature, and, from the precipitated solids, the xylene is removed by decantation 100 cm 3 of methanol are added, the crystals are filtered, the pH is adjusted to 8 by the addition of concentrated ammonium hydroxide, then 150 cm 3 of water are added, and the methanol is distilled off The aqueous phase is extracted with dichloromethane (3x50 cm 3 ) The combined organic phases are dried over anhydrous sodium sulfate, and evaporated to dryness 10 6 g of oily base are obtained which is purified by column chromatography using a mixture of toluene and methanol in a ratio of 8 2 An 1 4 g portion of the base obtained is converted to acid addition salt in a mixture of 10 cm 3 of ethyl acetate and 5 cm 3 of ether using isopropanol containing hydrogen chloride The salt is filtered and washed with a low amount of cold ether Thus, 1 35 g (87 %) of the title compound are obtained M p 173-175 °C Analysis for Cι 8 H 16 CI 2 F 3 N (374 23) calculated C 57 77 %, H 4 31 %, N 3 74 %, Cl 18 95 %, found C 57 30 %, H 4 30 %, N 3 69 %, Cl 18 80 % 1 H-NMR (CDCI 3 , 400 MHz) δ 15 81 (1 H, bs), 7 67 (1 H, d, J=7 6 Hz), 7 65 (1 H, s), 7 53 (2H, d, J=8 1 Hz), 7 43 (2H, d, J=8 1 Hz), 7 37 (1 H, d, J=8 3 Hz), 3 94 (2H, t, J=7 6 Hz), 3 68 (2H, t, J=7 6 Hz), 3 26 (2H, t, J=8 0 Hz), 3 01 (2H, t, J=8 0 Hz) Example 41 1-(4-Fluorostyryl)-4-methyl-6,7-methylenedιoxy-3,4-dιhydro- isoquinoline hydrochlonde To a solution of 3 27 g (0 01 moles) of N-/2-methyl-2-(3,4- methylenedιoxyphenyl)ethyl/-4-fluorocιnnamamιde in 50 cm 3 of absolute toluene, 4 66 g (0 05 moles) of phosphor(V) tpchloπde oxide are added under stirring, and the reaction mixture is stirred at 120 °C under an argon atmosphere till the end of the reaction Then, to the warm solution, 50 cm 3 of methanol are added, drop by drop, and the mixture is evaporated The residue is dissolved in methanol, then evaporated again This procedure is repeated 5 to 6 times, then the methanohc solution of the product is poured onto the ion exchanger Amberhst 46 resin The solution is evaporated, and diethyl ether is added The precipitated crystals are filtered Thus, 2 38 g (69 %) of the title compound are obtained M p decomposition above 200 °C 1H-NMR (DMSO-d 6 + CDCI 3 , 400 MHz) δ 14 02 (11-1, bs), 8 44 (1H, d, J=161 Hz), 785 (2H, m), 751 (1H, s), 743 (1H, d, J=161 Hz), 715 (2H, m), 697(1H, s), 620 (2H, s), 389(1H, ddd, Jι=145 Hz, J 2 =55 Hz, J 3 =350 Hz), 371 (1H, ddd, J,=145 Hz, J 2 =72 Hz, J 3 =41 Hz), 319 (1H, hx, J=89 Hz), 132 (3H, d, J=71 Hz) Example 42 1-(4-Fluorostyryl)-6,7-methylenedιoxy-4-propyl-3,4-dιhydro- isoquinohne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 74 % M p 184-185 °C 1H-NMR (CDCI 3 , 400 MHz) δ 1424 (1 H, bs), 842 (1 H, d, J=160 Hz), 779 (2H, m), 735 (1H, d, J=160 Hz), 732 (1H, s), 714 (2H, m), 687(1H, s), 617(2H, s), 404(1H, ddd.^148 Hz, J 2 =55 Hz, J 3 =1 Hz), 378 (1H, ddd, J,=148 Hz, J 2 =36 Hz, J 3 =26 Hz), 294 (1H, m), 125-160 (4H, m), 093 (3H, t, J=76 Hz) Example 43 4-Butyl-1-(4-fluorostyryl)-6,7-methylenedιoxy-3,4-dιhydro- isoquino ne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 67% Mp 163-166 °C 1H-NMR (DMSO-d 6 + CDCI 3 , 400 MHz) δ 1398 (1H, bs), 750 (1 H, s), 845 (1 H, d, J=158 Hz), 785 (2H, m), 742 (1 H, d, J=158 Hz), 715 (2H, m), 691 (1 H, s), 620 (2H, s), 400 (1 H, dd, Jι=148 Hz, J 2 =53 Hz), 379 (1H, dd, J,=148 Hz, J 2 =33 Hz), 295 (1H, m), 125-160 (6H, m), 090 (3H, t, J=76 Hz) Example 44 4-Ethyl-6,7-methylenedιoxy-1 -(4-trιfluoromethylstyryl)-3,4- dihydroisoquino ne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 60 % M p 162-165 °C 1H-NMR (DMSO-d 6 + CDCI 3 , 400 MHz) δ 14 10 (1 H, bs), 8 47 (1 H, d, J=16 1 Hz), 7 98 (2H, d, J=14 7 Hz), 7 70 (2H, d, J=14 7 Hz), 7 62 (1 H, d, J=16 1 Hz), 7 58 (1 H, s), 6 94 (1 H, s), 6 20 (2H, s), 4 05 (1 H, brdd, Jι=14 9 Hz, J 2 =5 5 Hz), 3 83 (1 H, d, Jι=14 9 Hz, J 2 =3 50 Hz), 2 93 (1 H, m), 1 63 (2H, m), 1 j01 (3H, t, J=7 6 Hz) Example 45 4-Butyl-6,7-methylenedιoxy-1 -(4-tπfluoromethylstyryl)-3,4- dihydroisoquinohne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 71 % M p 191 -193 °C 1H-NMR (DMSO-d 6 + CDCI 3 , 400 MHz) δ 14 10 (1 H, bs), 8 50 (1 H, d, J=16 2 Hz), 7 95 (2H, d, J=8 1 Hz), 7 70 (2H, d, J=8 1 Hz), 7 59 (1 H, d, J=16 2 Hz), 7 50 (1 H, s), 6 91 (1 H, s), 6 20 (2H, s), 4 04 (1 H, ddd, J 1 = 15 0 Hz, J 2 =5 5 Hz, J 3 = above 1 Hz), 382 (1H, ddd, J,=150 Hz, J 2 =35 Hz, J 3 =34 Hz), 297 (1H, m), 12 + 160 (6H, m), 09 (3H, J=76 Hz) Example 46 6,7-Methylenedιoxy-1-(4-methoxystyryl)-4-propyl-3,4-dιhydro- isoquinohne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 63 % M p 200-202 °C 1H-NMR (CDCIs, 400 MHz) δ 1402 (1H, bs), 847 (1H, d, J=160Hz), 774(2H, m), 732 (1H, s), 725 (1H, d, J=160 Hz), 695 (2H, m), 684 (1H, s), 616 (2H, s), 401 (1H, ddd, J,=148 Hz, J 2 =53 Hz, J 3 =26 Hz), 387 (3H, s), 375 (1H, ddd, J,=148 Hz, J 2 =36 Hz, J 3 =49 Hz), 291 (1H, m), 125 + 160 (4H, m), 092 (3H, t, 76 Hz) Example 47 6,7-Methylenedιoxy-4-propyl-1-(4-trιfluoromethylstyryl)-3,4- dihydroisoquino ne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 70% Mp 201-204 °C 1H-NMR (CDCI3, 400 MHz) δ 1453 (1H, bs), 845 (1H, d, J=161 Hz), 788 (2H, d, J=80 Hz), 769 (2H, d, J=80 Hz), 750 (1H, d, J=161 Hz), 732(1H, s), 688(11-1, s), 618 (2H, s), 405 (1H, dd, J 1= 150 Hz, J 2 =36 Hz), 381 (1H, dd, J=150 Hz, J 34 =56 Hz), 296 (1 H, m), 125 + 160 (4H, m), 093 (3H, t, J=76 Hz) Example 48 4-Methyl-6,7-methylenedιoxy-1-(4-methoxystyryl)-3,4-dιhydro- isoquinohπe hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 66 % M p 227-230 °C 1H-NMR (CDCIs, 400 MHz) δ 1408 (1H, bs), 847 (1H, d, J=160Hz), 774(2H, m), 733(11-1, s), 725 (1H, d, J=160 Hz), 695 (2H, m), 690 (1H, s), 616 (2H, s), 388 (1H, dd, J,=146 Hz, J 2 =76 Hz, J 3 =40 Hz), 387 (3H, s), 368 (1H, dd, Jι=146 Hz, J 2 =55 Hz, J 3 =36 Hz), 312 (1H, m), 130 (3H, d, J=70 Hz) Example 49 4-Butyl-1-(3,4-dιmethoxystyryl)-6,7-methylenedιoxy-3,4- dihydroisoquinohne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 58 % M p 206-208 °C 1H-NMR (CDCI 3 , 400 MHz) δ 1398 (1H, bs), 840 (1H, d, J=160 Hz), 739 (1H, dd, Jι=83 Hz, J 2 =20 Hz), 736 (1H, s), 733 (1H, d, J=160 Hz), 730 (1H, d, J=20 Hz), 691 (1H, d, J=83 Hz), 685 (1H, s), 617 (2H, s), 399 (1H, dd, ^=150 Hz, J 2 =54 Hz, J 3 =24 Hz), 398 (3H, s), 395 (3H, s), 375 (1H, Jι=150 Hz, J 2 =39 Hz, J 3 =46 Hz), 288 (1H, m), 120 + 160 (6H, m), 089 (3H, t, J=76 Hz) Example 50 4-Ethyl-1 -(4-fluorostyryl-6,7-methylenedιoxy-3,4-dιhydro- isoquinohne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 79 % M p 186-188 °C 1H-NMR (CDCI 3 , 400 MHz) δ 13 72 (1 H, bs), 8 40 (1 H, d, J=16 0 Hz), 7 88 (2H, m), 7 60 (1 H, s), 7 46 (1 H, d, J=16 0 Hz), 7 17 (2H, m), 6 95 (11-1, s), 6 21 (2H, s), 4 01 (1 H, dd, Jι=14 8 Hz, J 2 =5 54 Hz), 3 80 (1 H, dd, J,=14 8 Hz, J 2 =3 3 Hz), 2 92 (1 H, m), 1 62 (2H, m), 1 00 (3H, t, J=7 6 Hz) Example 51 4-Ethyl-6,7-methylenedιoxy-1 -(4-methoxystyryl)-3,4-dιrydro- isoquinoline hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 61 % M p 182-185 °C 1H-NMR (CDCI3, 400 MHz) δ 13 89 (1 H, bs), 7 33 (1 H, s), 8 44 (1 H, d, J=15 8 Hz), 7 75 (2H, m), 7 25 (1 H, d, J=15 8 Hz), 6 95 (2H, m), 6 87 (1 H, s), 6 16 (2H, s), 4 03 (1 H, m), 3 87 (3H, s), 3 76 (1 H, m), 2 82 (1 H, m), 1 63 (2H), 1 00 (3H, t, J=7 6 Hz) Example 52 1 -(4-Fluorostyryl)-4-hexyl-6,7-methylenedιoxy-3,4-dιhydro- isoquino ne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 71 % Mp 158-160 °C 1H-NMR(DMSO-d 6 +CDCI 3 , 400 MHz) δ 1418(11-1, bs), 843 (1H, d, J=162 Hz), 782 (2H, m), 740 (1H, s), 738 (1H, d, J=162 Hz), 714 (2H, m), 688(11-1, s), 619(2H, s), 400(1H, brdd, Jι=18 Hz, J 2 =55 Hz), 379 (1H, brdd, ^=148 Hz, J 2 =35 Hz), 294 (1H, m), 120 + 160 (10H, m), 087 (3H, t, J=76 Hz) Example 53 4-Hexyl-6,7-methylenedιoxy-1-(4-trιfluoromethylstyryl)-3,4- dihydroisoquinoline hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 80% Mp 171-173 °C 1H-NMR (DMSO-d 6 + CDCI 3 , 400 MHz) δ 1446 (1 H, bs), 848 (1 H, d, J=162 Hz), 792 (2H, d, J=80 Hz), 770 (2H, d, J=80 Hz), 755(1H, d, J=162 Hz), 740 (1H, s), 689(11-1, s), 620 (2H, s), 404 (1H, brdd, J 1= 149 Hz, J 2 =38 Hz), 382 (1H, brdd, Jι=149 Hz, J 2 =55 Hz), 295 (1H, m), 120 + 166 (10H, m), 088 (3H, t, J=76 Hz) Example 54 4-Hexyl-6,7-methylenedιoxy-1-(4-methoxystyryl)-3,4-dιhydro- isoquinohne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 74 % M p 129-131 °C 1H-NMR (CDCI 3 , 400 MHz) δ 14 02 (1 H, bs), 8 47 (1 H, d, J=15 7 Hz), 7 32 (1 H, s), 7 75 (2H, d, J=8 0 Hz), 7 25 (1 H, d, J=15 7 Hz), 6 95 (2H, d, J=8 0 Hz), 6 84 (1 H, s), 6 16 (2H, s), 3 87 (3H, s), 3 99 (1 H, m), 3 75 (1 H, m), 2 88 (1 H, m), 1 20 + 1.60 (10H, m), 0 88 (3H, t, J=7 6 Hz) Example 55 4-Butyl-6,7-methylenedιoxy-1 -(4-methoxystyryl)-3,4-dιhydro- isoquinohne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 67 % M p 140-142 °C H-NMR (CDCI3, 400 MHz) δ 13 95 (1 H, bs), 8 45 (1 H, d, J=15 8 Hz), 7 74 (2H, d, J=8 0 Hz), 7 32 (1 H, s), 7.25 H, d, J=15 8 Hz), 6 95 (2H, d, J=8 0 Hz), 6 85 (1 H, s), 6 16 (2H, s), 3.87 (3H, s), 4 00 (1 H, brdd, J,=14 8 Hz, J 2 =3 8 Hz), 3 76 (1 H, brdd, Jι=14 8 Hz, J 2 = 5 2 Hz), 2 89 (1 H, m), 1 20 + 1 60 (6H, m), 0 89 (3H, t, J=7 6 Hz) Example 56 1 -(3,4-Dιmethoxystyryl)-4-hexyl-6,7-methylenedιoxy-3,4- dihydroisoquino ne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 81 % M p 183-185 °C 1 H-NMR (DMSO-d 6 + CDCI 3 , 400 MHz) δ 13 25 (1 H, bs), 8 37 (1 H, d, J=158 Hz), 771 (1 H, s), 745 (1 H, d, J=20 Hz), 743 (1H, d, J=158 Hz), 741 (1H, dd, ^=82 Hz, J 2 =20 Hz), 696 (1 H, d, J=82 Hz), 693 (1 H, s), 622 (1 H, d, J=10 Hz), 621 (1H, d, J=10 Hz), 396 (3H, s), 394 (3H, s), 394 (1H, dd, Jι=149 Hz, J 2 =33 Hz), 376 (1H, dd, J,=149 Hz, J 2 =33 Hz), 376 (1H, dd, J,=149 Hz, J 2 =55 Hz), 298 (1H, m), 120-160 (10H, m), 087(3H, t J=76 Hz) Example 57 1 -(3,4-Dιmethoxystyryl)- 6,7-methylenedιoxy-4-propyl-3,4- dihydroisoquino ne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 70% Mp 212-215 °C 1H-NMR (CDCI 3 , 400 MHz) δ 1286(1H, s), 825(1H, d, J=158 Hz), 789 (1H, s), 756 (1H, d, J=20 Hz), 752 (1H, d, J=158 Hz), 738 (1H, dd, Jι = 16 Hz, J 2 =60 Hz), 708 (1H, s), 704 (1H, d, J=82 Hz), 625 (1 H, s), 624 (1 H, s), 392 (3H, s), 389 (3H, s), 386 (1H, brdd, J,=148 Hz, J 2 =53 Hz), 377 (1H, brdd, Jι=148 Hz, J 2 =28 Hz), 306 (1 H, m), 125 + 155 (4H, m), 09 (3H, t, J=76 Hz) Example 58 1 -(3,4-Dιmethoxystyryl)- 4-ethyl-6,7-methylenedιoxy-3,4- dihydroisoquino ne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 77% Mp 209-211 °C 1 H-NMR (CDCI 3 , 400 MHz) δ 13 87 (1 H, bs), 8 37 (1 H, d, J=15 9 Hz), 7 39 (1 H, dd, Jι=8 3 Hz, J 2 =2 0 Hz), 7 38 (1 H, s), 7 33 (1 H, d, J=15 9 Hz), 7 30 (1 H, d, J=2 0 Hz), 6 91 (1 H, d, J=8 3 Hz), 6 86 (1 H, s), 6 17 (2H, s), 4 02 (1 H, ddd, J,=15 0 Hz, J 2 =5 4 Hz), J 3 =2 3 Hz), 3 98 (3H, s), 3 95 (3H, s), 3 75 (1 H, ddd, Jι=15 0 Hz, J 2 =4 2 Hz, J 3 =4 2 Hz), 2 82 (1 H, m), 1 61 (2H, m), 1 00 (3H, t, J=7 6 Hz) Example 59 1 -(3,4-Dιmethoxystyryl)- 4-methyl-6,7-methylenedιoxy-3,4- dihydroisoquinohne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 63 % M p 201-203 °C 1H-NMR (CDCIs, 400 MHz) δ 13 91 (1 H, bs), 8 37 (1 H^d, J=15 8 Hz), 7 39 (1 H, dd, J=8 4 Hz, J=2 0 Hz), 7 38 (1 H, s), 7 32 (1 H, d, J=15 8 Hz), 7 30 (1 H, d, J=2 0 Hz), 6 91 (1 H, d, J=8 4 Hz), 6 91 (1 H, s), 6 16 (2H, s), 3 98 (3H, s), 3 95 (3H, s), 3 87 (1 H, ddd, J,=14 8 Hz, J 2 =7 5 Hz, J 3 =2 5 Hz), 3 67 (1 H, ddd, Jι=14 8 Hz, J 2 =5 2 Hz, J 3 =1 8 Hz), 3 12 (1 H, m), 1 30 (3H, d, J=7 0 Hz) Example 60 4-Methyl-6,7-methylenedιoxy-1 -(4-trιfluoromethylstyryl)-3,4- dihydroisoquinohne hydrochlonde The procedure described in Example 41 is followed to obtain the title compound Yield 61 % M p 216-218 °C 1H-NMR (DMSO-d 6 + CDCI 3 , 400 MHz) δ 14 18 (1 H, bs), 8 48 (1 H, d, J=16 0 Hz), 7 98 (2H, s), 7 70 (2H, s), 7 63 (1 H, d, J=16 0 Hz), 7 59 (1 H, s), 6 99 (1 H, s), 6 21 (2H, s), 3 93 (1 H, dd, Jι=14 6 Hz, J 2 =5 7 Hz), 3 74 (1 H, dd, J,=14 6 Hz, J 2 =5 2 Hz), 3 22 (1 H, m), 1 34 (3H, d, J=7 0 Hz) Example 61 1 -(4-Fluorostyryl)-6,7-methylenedιoxy-3,4-dιhydroιsoquιnohne hydrochlonde 12 5 g of N-/2-(3,4-methylenedιoxyphenyl)ethyl/-4-fluoro- αnnamamide are dissolved in 100 cm 3 of benzene, and, to the solution obtained, 25 cm 3 of phosphor(V) trichloride oxide are poured The reaction mixture is boiled for 1 5 hours, then cooled to 10 °C and stirred at this temperature for 1 hour The crystalline crude product is filtered, washed with a small amount of benzene cooled to 10 °C, and recrystalhzed from 400 cm 3 of 2-propanol Thus, 7 1 g (53 7 %) of the title compound are obtained M p 219-221 °C H-NMR (DMSO-d 6 , 200 MHz) δ 12 55 (1 H, bs), 8 3 (1 H, d, J=16 1 Hz), 7 96 (2H, m), 7 87 (1 H, s), 7 60 (1 H, d, J=16 1 Hz), 7 37 (2H, t, J=9 Hz), 7 17 (1 H, s), 6 25 (2H, s), 3 79 (2H, t, J=8 0 Hz), 3 04 (2H, t, J=8 0 Hz) Example 62 1 -(4-Trιfluoromethylstyryl)-6,7-methylenedιoxy-3,4-dιhydro- isoquinohne hydrochlonde 20 g (0 055 moles) of 2-(3,4-methylenedιoxyphenyl)ethyl-N-(4- trιfluoromethyl)cιnnamamιde are boiled in 70 cm 3 of benzene in the presence of 20 cm 3 of phosphor(V) trichloride oxide for 3 5 hours The reaction mixture is cooled to 20 °C, the precipitated salt is washed with some hexane, and recrystalhzed from 110 cm 3 of ethanol Thus, 7 2 g (72 %) of the title compound are obtained M p 208-212 °C Analysis for Cι 9 Hι 5 CIF 3 N0 2 (381 70) calculated C 59 78 %, H 3 96 %, Cl 9 29 %, N 3 67 %, found C 59 74 %, H 3 94 %, Cl 9 22 %, N 3 61 % 1 H-NMR (DMSO-d 6 , 200 MHz) δ 12 56 (11-1, bs), 8 23 (1 H, d, J=16 1 Hz), 8 09 (2H, d, J=8 1 Hz), 7 89 (1 H, s), 7 88 (2H, d, J=8 1 Hz), 7 78 (1 H, d, J=16 1 Hz), 7 2 (1 H, s), 6 26 (2H, s), 3 82 (2H, t, J=8 1 Hz), 3 09 (2H, d, J=8 1 Hz) Example 63 6,7-Ethylenedιoxy-1 -/2-(4-trιfluoromethylpheπyl)ethyl/-4-propyl- 3,4-dιhydroιsoquιnohne oxalate To a solution of 7 5 g (0 017 moles) of N-/2-(3,4-ethylenedιoxy- phenyl)ethyl/-3-(4-trιfluoromethylphenyl)propιonyl amide in 100 cm 3 of absolute benzene, 6 cm 3 of phosphor(V) trichloride oxide are added The reaction mixture is boiled for 3 hours, then evaporated under reduced pressure From the residue, 3x75 cm 3 of methanol and 75 cm 3 of benzene are distilled off The crude product is dissolved in 200 cm 3 of dichloromethane, to the solution obtained, crushed ice and 20 % aqueous sodium hydroxide solution are added under intensive stirring until the pH value of the aqueous phase remains 10 to 11 After half an hour's stirring, the phases are separated The aqueous phase is extracted twice using 80 cm 3 of dichloromethane each time The combined organic phases are dried over anhydrous sodium sulfate and evaporated to dryness The residual crude product is purified by column chromatography to obtain 4 8 * g of base that is converted to the oxalate salt in absolute diethyl ether Thus, 5 7 g (69 %) of the title compound are obtained M p 122-125 °C 1 H-NMR (DMSO-d 6 + CDCI 3 , 400 MHz) δ 7 63 (2H, d, J=8 1 Hz), 7 54 (1 H, s), 7 45 (2H, d, J=8 1 Hz), 6 88 (1 H, s), 4 37 (2H, m), 4 30 (2H, m), 3 69 (1 H, dd, J,=3 1 Hz, J 2 =15 4 Hz), 3 58 (1 H, dd, Jι=5 3 Hz, J 2 =14 9 Hz), 3 43 (1 H, m), 3 14 (2H, m), 3 01 (1 H, m), 2 75 (1 H, m), 1 23 (1 H, m), 1 11 (3H, m), 0 79 (3H, t, J=6 6 Hz) IR (KBr, cm 1 ) 3420, 2700, 1750, 1648, 1328 Example 64 6,7-Ethylenedιoxy-1 -/(4-trιfluoromethyl)styryl/-4-propyl-3,4- dihydroisoquinohne oxalate To a solution of 6 8 g (0 016 moles) of N-/2-propyl-2-(3,4- ethylenedιoxyphenyl)ethyl/-4-trιfluoromethylcιnnamamιde in 70 cm 3 of absolute benzene, 6 cm 3 of phosphor(V) trichloride oxide are added The reaction mixture is boiled for 2 hours, then evaporated From the residue, 3x60 cm3 of methanol are distilled off, 100 cm 3 of ether are added, the mixture is stirred and boiled for 15 minutes, then the ether is removed by decantation, and this procedure is repeated twice. The crude product obtained is dissolved in dichloromethane and the pH is adjusted to 11 by the addition of 20 % aqueous sodium hydroxide solution under stirring The separated aqueous phase is extracted with dichloromethane twice using 50 cm 3 of dichloromethane each time The combined organic phases are dried over anhydrous sodium sulfate, evaporated to obtain 2.9 g (45 %) of oily product The crude product is dissolved in absolute ether, and, to the solution, an equimolar amount of anhydrous oxalic acid is added The crystalline salt is filtered. Thus, 3 22 g (41 %) of the title compound are obtained. M.p/ 140-143 °C Example 65 7-Hydroxy-1 -/2-(4-tπfluoromethylphenyl)ethyl/-6-methoxy-3,4- dihydroisoquinohne A solution of 30 g (0 082 moles) of 1 -/2-(4-trιfluoromethyl- phenyl)ethyl/-6,7-dιmethoxy-3,4-dιhydroιsoquinohne in 250 cm 3 of concentrated hydrochloric acid is stirred under nitrogen stream over an oil bath of 120 °C for 50 hours The solution is cooled in ice water, the crystalline matter is filtered, then dissolved in 300 cm 3 of methanol By the addition of 100 cm 3 of concentrated aqueous ammonia, the base is liberated. From the precipitated gummy matter the solvent is removed by decantation The residue is recrystalhzed from acetonitnle. Thus, 11 7 g (33 %) of the title compound are obtained M p 129-132 °C Example 66 1 -(2-Phenylethyl)-6,7-methylenedιoxy-3,4-dιhydroιsoquιnohne A solution of 10 g (0 033 moles) of N-/2-(3,4-methylenedιoxy- phenyl)ethyl/-3-phenylpropιonyl amide and 30 cm 3 of phosphor(V) trichloride oxide in 70 cm 3 of absolute benzene is boiled for 1 5 hours, then cooled to 50 °C, and the precipitated crystals are filtered The crude hydrochlonde is dissolved in a mixture of 200 cm 3 of water and 200 cm 3 of methanol, the pH value of the solution is adjusted to 13 by the addition of 20 % aqueous sodium hydroxide solution The precipitated white crystalline base is filtered, washed with cold water, dried, and recrystalhzed from a mixture of ethanol and water Thus, 5 3 g (58 %) of the title compound are obtained M p 112-115 °C Example 67 A) 4,6-Dιmethoxy-1 -styryl-4-tπfluoromethyl-3,4-dιhydro isoquinohnium maleate A mixture of 3 79 (10 mmoles) of N-cιnnamoyl-3,3,3-trιfluoro-2- methoxy-2-(3-methoxyphenyl)propylamιne and 4 46 cm 3 (7 67 g, 50 mmoles) of phosphor(V) trichloride oxide is stirred at 85 °C for 16 hours The reaction mixture cooled to room temperature is poured onto 40 cm 3 of ice water The pH is adjusted to 11 by the addition of concentrated aqueous ammonia The mixture is extracted three times using 30 cm 3 of ethyl acetate each time The combined organic phases are dried over anhydrous magnesium sulfate, and evaporated The crude base is dissolved in 10 cm 3 of methanol, and, to the solution obtained, a solution of 1 16 g (10 moles) of maleic acid in 10 cm 3 of methanol, then 40 cm 3 of diisopropyl ether are added, drop by drop The precipitated crystals are filtered, washed with 10 cm 3 of diisopropyl ether Thus, 2 54 g (53 %) of the title compound are obtained M p 149-151 °C (ethanol-dnsopropyl ether) Analysis for C 24 Hι 2 F 3 N0 6 (477 4) calculated C 60 38 %, H 4 64 %, N 2 93 %, found C 60 50 %, H 4 56 %, N 3 03 % IR (film, cm 1 ) 1600, 1493, 1252, 1177 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 14 (1 H, d, J=8 8 Hz), 7 86 (2H, dd, J=8 7 Hz, J=5 7 Hz), 7 57 (1 H, d, J=15 8 Hz), 7 50- 7 40 (3H, m), 7 13 (1 H, d, J=3 0 Hz), 6 21 (2H, s), 4 24 (2H, s), 3 92 (3H, s), 3 30 (3H, s) B) 4,6-Dιmethoxy-1 -styryl-4-tπfluoromethyl-3,4-dιhydro- isoquinohnium chloride 3 61 g of the crude base are dissolved in 40 cm 3 of diisopropyl ether, then 1 73 cm 3 of isopropanol containing 25 3 g/100 cm 3 of hydrogen chloride (12 moles) are added, drop by drop The precipitated crystals are filtered, washed with 10 cm 3 of diisopropyl ether Thus, 2 1 1 g (53 %) of the title compound are obtained M p 188 °C (ethanol) Analysis for C 2 oHι 9 CIF 3 N0 2 (397 82) calculated C 60 38 %, H 4 81 %, Cl 8 91 %, N 3 54 %, found C 60 24 %, H 4 84 %, Cl 8 92 %, N 3 49 % IR (film, cm '1 ) 3435, 1508, 1477 1 H-NMR (DMSO-d 6 + CDCI 3 , 400 MHz) δ 8 49 (1 H, d, J=8 9 Hz), 8 22 (1 H, m), 7 88 (2H, dd, J=7 6 Hz, J=1 8 Hz), 7 73 (1 H, d, J=16 1 Hz), 7 53 (3H, m), 7 35 (1 H, dd, J=8 9 Hz, J=2 6 Hz), 7 29 (1 H, d, J=2 6 Hz), 6 60 (1 H, bs), 4 42 (1 H, d, J=16 0 Hz), 4 26 (1 H, d, J=16 0 Hz), 4 04 (3H, s), 3 42 (3H, s) 3C-NMR (DMSO-d 6 + CDCI 3 , 100 6 MHz) δ 166 9, 166 6, 149 6, 135 7, 134 2, 133 7, 132 3, 129 8, 129 3, 124 4 (q, 1 J CF =287 5 Hz), 1 19 0, 1 15 9, 1 15 8, 1 14 7 75 0 (q, 2 J CF =28 5 Hz), 55 8, 53 3, 42 2 Example 68 A) 1 -(4-Fluorostyryl)-4,6-dιmethoxy-4-trιfluoromethyl-3,4- dihydroisoquinohnium maleate 3 97 g (10 mmoles) of N-(4-fluorocιnnamoyl)-3,3,3-trιfluoro-2- methoxy-2-(3-methoxyphenyl)propylamιne are reacted with 4 46 cm 3 (7 67 g, 50 mmoles) of phosphor(V) trichloride oxide in the manner described in Example 67, section A) The crude base obtained is recrystalhzed from hexane Thus, 2 54 g (67 %) of drab coloured 1 -(4-fluorostyryl)-4,6-dιmethoxy-4-tπfluoro- methyl-3,4-dιhydroιsoquιnohne are obtained M p 92-93 °C (hexane) Analysis for C 20 Hι 7 F 4 NO 2 (379 35) calculated C 63 32 %, H 4 52 %, N 3 69 %, found C 63 05 %, H 4 48 %, N 3 61 % IR (KBr, cm ) 2959, 1646, 1510, 1180 1H-NMR (DMSO-d 6 , 400 MHz) δ 7 70 (1 H, d, J=8 6 Hz), 7 53 (2H, m), 7 42 (1 H, d, J=15 9 Hz), 7 24 (1 H, d, J=2 6 Hz), 7 14 (1 H, d, J=15 9 Hz), 7 10-7 02 (3H, m), 4 26 (1 H, d, J=17 2 Hz), 4 17 (1 H, d, J=17 2 Hz), 3 90 (3H, s), 3 32 (3H, s) 1 3 C-NMR (CDCI 3 , 100 6 MHz) δ 163 1 (d, 1 J CF =249 1 Hz), 161 8, 161 6, 135 5, 132 6, 132 4, 129 0 (d, 3 J CF =8 4 Hz), 128 1 , 125 2 (q, 1 J CF =286 1 Hz), 123 6 (d, 4 J CF =2,3 Hz), 123 0, 115 8 (d, 2 J CF =22 1 Hz), 114 8, 112 8, 75 1 (q, 2 J CF =27 5 Hz), 55 6, 52 6, 49 4 1 90 g (5 mmoles) of the base obtained are dissolved in 7 cm 3 of methanol To the solution obtained, a solution of 0 58 g (5 mmoles) of maleic acid in 7 cm 3 of methanol, then 20 cm 3 of diisopropyl ether are added, drop by drop The precipitated crystals are filtered, and washed with 7 cm 3 of diisopropyl ether Thus, 1 66 g (67 %) of the title compound are obtained in the form of yellow solids M p 139-140 °C (ethanol-dnsopropyl ether) Analysis for C 24 H 21 F 4 N0 6 (495 43) calculated C 58 19 % H 4 27 %, N 2 83 %, found C 57 91 %, H 4 28 %, N 2 87 % IR (KBr, cm 1 ) 1600, 1350, 1253, 1179 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 16 (1 H, d, J=8 8 Hz), 7 90- 7 80 (2H m), 7 58 (2H, s), 7 40-7 20 (3H, m), 7 20-7 10 (1 H, m), 6 21 (2H, s), 4 25 (2H, s), 3 93 (3H, s), 3 31 (3H, s) B) 1 -(4-Fluorostyryl)-4,6-dιmethoxy-4-trιfluoromethyl-3,4- dihydroisoquinohnium chloride 1 14 g (3 mmoles) of 1 -(4-fluorostyryl)-4,6-dιmethoxy-4- trιfluoromethyl-3,4-dιhydroιsoquιnohπe are reacted with 0 5 cm 3 of 2-propanol containing 3 6 mmoles (25 3 g/100 cm 3 ) of hydrogen chloride in the manner described in Example 67, section B) Thus, 0 94 g (75 %) of the title compound are obtained in the form of pale yellow solids M p 213-214 °C (ethanol, decomposition) Analysis for C 20 Hι 8 CIF 4 NO 2 (415 81 ) calculated C 57 77 %, H 4 36 %, Cl 8 53 %, N 3 37 %, found C 57 54 %, H 4 31 %, Cl 8 57 %, N 3 40 % IR (film, cm ) 2541 , 1599, 1241 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 51 (1 H, d, J=8 8 Hz), 8 16 (1 H, d, J=15 8 Hz), 8 05-7 96 (2H, m), 7 77 (1 H, d, J=15 8 Hz), 7 50-7 30 (3H, m), 7 25 (1 H, s), 4 49 (11-1, d, J=16 1 Hz), 4 25 (1 H, d, J=16 1 Hz), 4 02 (3H, s), 3 39 (3H, s) Example 69 A) 4,6-Dιmethoxy-4-(trιfluoromethyl)-1 -(4-trιfluoromethyl- styryl)-3,4-dιhydroιsoquιnolιnιum maleate The procedure described in Example 67, section A) is followed starting from 4 47 g (10 mmoles) of N-(4-trιfluoromethyl- cιnnamoyl)-3,3,3-tπfluoro-2-methoxy-2-(3-methoxyphenyl)- propylamine The crude base is recrystalhzed from hexane Thus, 3 09 g (72 %) of drab coloured 4,6-dιmethoxy-4- (trιfluoromethyl)-1 -(4-trιfluoromethylstyryl)-3,4-dιhydro- isoquinohne are obtained M p 87-88 °C (hexane) Analysis for C 2 ιHι 7 F 6 N0 2 (429 36) calculated C 58 75 %, H 3 99 %, N 3 26 %, found C 58 58 %, H 3 95 %, N 3 30 % IR (KBr, cm '1 ) 1608, 1325, 1166 1 H-NMR (CDCI 3 , 400 MHz) δ 7 69 (1 H, d, J=8 7 Hz), 7 67-7 61 (4H, m), 7 48 (1 H, d, J=15 9 Hz), 7 30 (1 H, d, J=15 9 Hz), 7 25 (1 H, d, J=2 4 Hz), 7 04 (1 H, dd, J=8 7 Hz, J=2 4 Hz), 4 28 (1 H, d, J=17 5 Hz), 4 18 (1 H, d, J=17 5 Hz), 3 91 (3H, s), 3 33 (3H, s) 13 C-NMR (CDCI 3 , 100 6 MHz) δ 161 9, 161 4, 139 7, 135 1 , 132 8, 130 5 (q, 2 J CF =32 4 Hz), 128 0, 127 5, 126 3, 125 4 (q, 1 J CF =293 8 Hz), 125 8 (q, 3 J CF =3 8 Hz), 124 0 (q, 1 J CF =272 0 Hz), 122 8, 1 14 9, 1 12 9, 75 1 (q, 2 J CF =27 8 Hz), 55 6, 52 6, 49 6 2 15 g (5 mmoles) of the base obtained is converted to the maleate in the manner described in Example 68 Thus, 1 96 g (72 %) of the yellow title compound are obtained M p 139-140 °C (ethanol-dnsopropyl ether) Analysis for C 25 H 2 ιF 6 N0 6 (545 44) calculated C 55 05 %, H 3 88 %, N 2 57 %, found C 55 18 %, H 3 80 %, N 2 69 % IR (KBr, cm 1 ) 1605, 1335, 1252, 1168 1 H-NMR (CDCI3, 400 MHz) δ 8 14 (1 H, d, J=8 8 Hz), 8 04 (1 H, s), 8 00 (1 H, s), 7 81 (1 H, s), 7 74 (2H, d, J=8 4 Hz), 7 60 (1 H, d, J=16 1 Hz), 7 35-7 20 (1 H, m), 7 14 (1 H, s), 6 25 (2H, s), 4 26 (2H, s), 3 92 (3H, s), 3 30 (3H, s) B) 4,6-Dιmethoxy-4-(trιfluoromethyl)-1 -(4-tπfluoromethyl- styryl)-3,4-dιhydroιsoquιnohnιum chloride 1 29 g (3 mmoles) of the base obtained as described in section A) are reacted with 0 5 cm 3 of 2-propanol containing 25 3 g/100 cm 3 (3 6 mmoles) of hydrogen chloride in the manner described in Example 67, section B) Thus, 0 86 g (72 %) of the pale yellow title compound are obtained M p 234-235 °C (ethanol decomposition) Analysis for C ιHι 8 CIF 6 N0 2 calculated C 54 15 %, H 3 89 %, Cl 7 61 %, N 3 01 %, found C 53 94 %, H 3 86 %, Cl 7 57 %, N 2 99 % IR (film, cm 1 ) 1599, 1423, 1252 1 H-NMR (DMSO-d 6 , 200 MHz) δ 8 56 (1 H, d, J=8 9 Hz), 8 31 (1 H, d, J=16 1 Hz), 8 13 (2H, d, J=8 2 Hz), 7 94 (1 H, d, J=16 1 Hz), 7 90 (2H, d, J=8 2 Hz), 7 43 (1 H, dd, J=8 9 Hz, J=2 4 Hz), 7 26 (1 H, bs), 4 54 (1 H, d, J=16 5 Hz), 4 27 (1 H, d, J=16 5 Hz), 4 03 (3H, s), 3 4 (3H, s) Example 70 A) 4,6-Dιmethoxy-1 -(4-nιtrostyryl)-4-trιfluoromethyl-3,4- dihydroisoquinolinium maleate The procedure described in Example 67, section A) is followed starting from 4 24 g (10 mmoles) of N-4-nιtrocιnnamoyl-3,3,3- trιfluoro-2-methoxy-2-(3-methoxyphenyl)propylamιne The crude base is recrystalhzed from hexane Thus, 2 58 g (63 %) of drab coloured 4,6-dιmethoxy-1 -(4-nιtrostyryl)-4-tπfluoro- methyl-3,4-dιhydroιsoquιnohne are obtained M p 146-147 °C (hexane) Analysis for C 2 oHι 2 F 3 N 2 0 4 (406 36) calculated C 59 11 %, H 4 22 %, N 6 89 %, found C 58 87 %, H 4 24 %, N 6 83 % IR (KBr, cm 1 ) 1612, 1514, 1313, 1178 1H-NMR (CDCI 3 , 200 MHz) δ 8 24 (2H, dd, J=8 8 Hz, J=1 9 Hz), 7 75-7 65 (3H, m), 7 53 (1 H, d, J=15 9 Hz), 7 37 (1 H, d, J=15 9 Hz), 7 25 (1 H, d, J=2 6 Hz), 7 06 (1 H, dd, J=8 3 Hz, J=2 6 Hz), 4 32 (1 H, d, J=17 6 Hz), 4 18 (1 H, d, J=17 7 Hz), 3 92 (3H, s), 3 34 (3H, s) 2 03 g (5 mmoles) of the base obtained are converted to the maleate salt in the manner described in Example 68 Thus, 1 65 g (63 %) of the yellow title compound are obtained M p 168-170 °C (ethanol-dnsopropyl ether) Analysis for C 24 H 21 F 3 N 2 0 8 (522 44) calculated C 55 18 %, H 4 05 %, N 5 36 %, found C 55 32 %, H 4 07 %, N 5 26 % IR (KBr, cm '1 ) 1599, 1251 , 1 176 1 H-NMR (CDCI3, 200 MHz) δ 8 32 (2H, d, J=8 8 Hz), 7 97 (1 H, d, J=8 8 Hz), 7 86 (1 H, s), 7 82 (1 H, s), 7 58 (1 H, d, J=16 0 Hz), 7 40-7 37 (1 H, m), 7 27 (1 H, m), 7 25-7 15 (1 H, m), 6 37 (2H, s), 4 33 (2H, d, J=7 4 Hz), 4 03 (3H, s), 3 45 (3H, s) B) 4,6-Dιmethoxy-1 -(4-nιtrostyryl)-4-trιfluoromethyl-3,4- dihydroisoquinohnium chloride 1 22 g (3 mmoles) of the base obtained as described under section A) are reacted with 0 5 cm 3 of 2-propanol containing 25 3 g/100 cm 3 (3 6 mmoles) of hydrogen chloride in the manner described in Example 67 section B) Thus, 0 90 g (68 %) of the pale yellow title compound are obtained M p 245-246 °C (ethanol, decomposition) Analysis for C 20 Hι 8 CIF 3 N 2 O 4 (442 82) calculated C 54 25 %, H 4 10 %, Cl 8 01 %, N 6 33 % found C 54 14 %, H 4 08 %, Cl 8 07 %, N 6 23 % IR (film, cm 1 ) 1 599, 1345, 1250, 1 181 1 H-NMR (DMSO-d 6 , 200 MHz) δ 8 48 (1 H, d, J=8 8 Hz), 8 36 (1 H, d, J=8 8 Hz), 8 24-8 06 (4H, m), 7 97 (1 H, d, J=16 1 Hz), 7 40 (1 H, dd, J=8 8 Hz, J=2 2 Hz), 7 25 (1 H, s), 4 51 (1 H, d, J=16 5 Hz), 4 02 (1 H, d, J=16 5 Hz), 4 02 (3H, s), 3 38 (3H, s) Example 71 6,7-Methylenedιoxy-4-methoxy-4-trιfluoromethyl-1-(4-tπfluoro- methylstyryl)-3,4-dιhydroιsoquιnohnιum chloride The procedure described in Example 67, section A) is followed starting from 4 61 g (10 mmoles) of N-(4-trιfluoromethyl- cιnnamoyl)-3,3,3-trιfluoro-2-methoxy-2-(3,4-methylenedιoxy- phenyl)propylamιne The crude base is recrystalhzed from hexane Thus, 2 44 g (55 %) of drab coloured 6,7- methylenedιoxy-4-methoxy-4-tπfluoromethyl-1 -(4- trιfluoromethylstyryl)-3,4-dιhydroιsoquιnohne are obtained M p 87-88 °C (hexane) Analysis for C 2 ιH 15 F 6 N0 3 (443 35) calculated C 56 89 %, H 3 41 %, N 3 16 %, found C 56 71 %, H 3 39 %, N 3 22 % IR (KBr, cm 1 ) 1579, 1389, 1 167 1 H-NMR (CDCI3, 400 MHz) δ 7 70-7 60 (4H, m), 7 46 (1 H, d, J=15 9 Hz), 7 24 (1 H, d, J=15 9 Hz), 7 19 (1 H, s), 7 18 (1 H, s), 6 15 (11-1, d, J=1 3 Hz), 6 09 (1 H, d, J=1 3 Hz), 4 26 (1 H, d, J=17 7 Hz), 4 16 (1 H, d J=17 7 Hz), 3 30 (3H, s) 13 C-NMR (CDCI 3 , 100 6 MHz) δ 161 0, 150 1 , 148 9, 139 5, 135 4, 130 6 (q, 2 J C F=32 4 Hz), 127 5, 126 1 , 125 7 (q, 3 J CF =5 4 Hz), 125 6, 125 3 (q, 1 J CF =287 3 Hz), 124 5, 124 0 (q, 1 J CF =272 0 Hz), 107 6, 106 4, 102 1 , 75 2 (q, 2 J CF =27 5 Hz), 52 4, 49 6 1 33 g (3 mmoles) of the base obtained above are reacted with 0 5 cm 3 of 2-propanol containing 25 3 g/100 cm 3 (3 6 mmoles) of hydrogen chloride Thus, 1 05 g (73 %) of the pale yellow title compound are obtained M p 248-250 °C (acetone, diisopropyl ether, decomposition) Analysis for C 2 ιHι 6 CIF 8 N0 3 (479 81) calculated C 52 57 %, H 3 36 %, Cl 7 39 %, N 2 92 %, found C 52 61 %, H 3 38 %, Cl 7 38 %, N 2 94 % IR (film, cm "1 ) 1623, 1514, 1394, 1325, 1 171 , 1 126 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 15-8 05 (4H, m), 7 90-7 80 (3H, m), 7 32 (1 H, m), 6 37 (1 H, d, J=0 9 Hz), 6 34 (1 H, d, J=0 9 Hz), 4 45 (1 H, d, J=17 0 Hz), 4 24 (1 H, d, J=17 0 Hz), 3 60 (1 H, bs), 3 35 (3H, s) Example 72 4,6-Dιmethoxy-4-trιfluoromethyl-1 -(2-(4-trιfluoromethylphenyl)- ethyl/-3,4-dιhydroιsoquιnohnιum chloride The procedure described in Example 67, section A) is followed starting from 1 12 g (2 5 mmoles) of N-/3-(4-trιfluoromethyl- phenyl)propanoyl/-3,3,3-tπfluoro-2-methoxy-2-(3-methoχy- phenyl)propylamιne and 2 0 cm 3 (3 36 g, 22 mmoles) of phosphor(V) trichloride oxide The crude base is dissolved in 10 cm 3 of diisopropyl ether, and, to the solution formed, 0 4 cm 3 of 2-propanol containing 25 3 g/100 cm 3 (3 mmoles) of hydrogen chloride are added, drop by drop Thus, 0 96 g (82 %) of the colourless title compound are obtained M p 185-187 °C (decomposition, ethanol) Analysis for C 21 H 20 CIF 6 NO 2 (467 84) calculated C 53 91 %, H 4 31 %, Cl 7 58 %, N 2 99 %, found C 53 72 %, H 4 30 %, Cl 7 56 %, N 2 97 % IR (film, cm ') 2494, 1666, 1328, 1252 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 38 (1 H, d, J=8 8 Hz), 7 66 (2H, d, J=8 5 Hz), 7 59 (2H, d, J=8 5 Hz), 7 36 (1 H, dd, J=8 8 Hz, J=2 4 Hz), 7 20 (11-1, s), 4 42 (1 H, d, J=16 3 Hz), 4 19 (1 H, d, J=16 3 Hz), 3 99 (3H, s), 3 75-3 40 (2H, m), 3 31 (3H, s), 3 20-3 00 (2H, m) 13 C-NMR (DMSO-d 6 , 50 3 MHz) δ 175 0, 166 0, 144 1 , 134 8, 132 8, 129 6, 127 5 (q, 2 J CF =31 7 Hz), 125 3 (q, 3 J CF =3 8 Hz), 124 5 (q, 1 J CF =270 2 HZ), 124 3 (q, 1 J CF =287 4 Hz), 118 6, 116 0, 114 2, 74 8 (q, 2 J CF =28 2 Hz), 56 7, 52 9, 42 4, 33 4, 33 0 Example 73 1 -/2-(4-Fluorophenyl)ethyl/-4,6-dιmethoxy-4-trιfluoromethyl-3,4- dihydroisoquinolinium chloride The procedure described in Example 67, section A) is followed starting from 1 00 g (2 5 mmoles) of N-/3-(4-fluorophenyl)- propanoyl/-3,3 3-tπfluoro-2-methoxy-2-(3-methoxyphenyl)- propylamine and 2 0 cm 3 of phosphor(V) trichloride oxide The crude base is dissolved in 10 cm 3 of diisopropyl ether, and, to the solution formed, 0 4 cm 3 of 2-propanol containing 25 3 g/100 cm 3 (3 mmoles) of hydrogen chloride are added, drop by drop Thus, 0 86 g (82 %) of the colourless title compound are obtained M p 190-191 °C (ethanol, decomposition) Analysis for C 2 oH 20 CIF 4 N0 2 (417 84) calculated C 57 49 % H 4 82 %, Cl 8 48 %, N 3 35 %, found C 57 44 %, H 4 83 %, Cl 8 58 %, N 3 42 % IR (film, cm "1 ) 1602, 1512 1254 1 177 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 37 (1 H, d, J=8 6 Hz), 7 40- 7 35 (3H, m), 7 20 (1 H, d, J=2 3 Hz), 7 14 (2H, t, J=8 8 Hz), 4 41 (1 H, d, J=16 7 Hz), 4 20 (1 H, d, J=16 7 Hz), 4 00 (3H, s), 3 70-3 30 (2H, m), 3 31 (3H, s), 3 00-2 85 (2H, m) 1 3 C-NMR (DMSO-d 6 , 50 3 MHz) δ 175 6, 166 2, 161 2 (d, 1 J CF =241 9 Hz), 135 3, 135 0, 132 8, 130 6 (d, 3 J CF =8 0 Hz), 124 3 (q, 1 JC F =287 6 Hz), 118 5, 116 1 , 115 3 (d, 2 J CF = 21 4 Hz), 114 3, 74 8 (q, 2 J CF =28 0 Hz), 56 8, 53 0, 42 1 , 33 5, 33 2 Example 74 6,7-Methylenedιoxy-4-methoxy-4-trιfluoromethyl-1 -/2-(4- trιfluoromethylphenyl)ethyl/-3,4-dιhydroιsoquιπohnιum chloride The procedure described in Example 67, section A) is followed to obtain the title compound as colourless solids Yield 75 % M p 196-197 °C (ethanol, decomposition) Analysis for C 2 ιHι 8 CIF 6 N0 3 (481 83) calculated C 52 35 %, H 3 77 %, Cl 7 36 %, N 2 91 %, found C 52 16 %, H 3 79 %, Cl 7 33 %, N 2 90 % IR (film, cm ) 2494, 1666, 1328, 1252 1 H-NMR (DMSO-de 400 MHz) δ 7 95 (1 H, s), 7 67 (2H, d, J=8 2 Hz), 7 58 (2H, d, J=8 2 Hz), 7 28 (1 H, s), 6 34 (2H, d, J=14 9 Hz), 4 36 (1 H, d J=16 8 Hz), 4 16 (1 H, d, J=16 8 Hz), 3 80-3 35 (2H, m), 3 27 (3H, s), 3 15-2 90 (2H, m) Example 75 1-/2-(4-Fluorophenyl)ethyl/-6,7-methylenedιoxy-4-methoxy-4- trιfluoromethyl-3,4-dιhydroιsoquιnohnιum chloride The procedure described in Example 67, section A) is followed to obtain the title compound as colourless solids Yield 80 % M p 195-196 °C (ethanol, decomposition) Analysis for C 20 Hι 8 CIF 4 NO 3 (431 82) calculated C 55 63 %, H 4 20 %, Cl 8 21 %, N 3 24 %, found C 55 36 %, H 4 24 %, Cl 8 20 %, N 3 27 % IR (film, cm 1 ) 1671 , 1608 1512, 1300, 1179 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 07 (1 H, s), 7 45-7 35 (2H, m), 7 32 (1 H, s), 7 14 (2H, t, J=8 8 Hz), 6 37 (2H, d, J=3 7 Hz), 4 44 (1 H, d, J=17 1 Hz), 4 15 (1 H, d, J=17 1 Hz), 3 70-3 30 (2H, m), 3 30 (3H, s), 3 05-2 95 (2H, m) 13 C-NMR (DMSO-d 6 , 100 6 MHz) δ 175 8, 161 2 (d, 1 J CF =242 2 Hz), 155 0, 150 1 , 135 2 (d, 4 J CF =3 1 Hz), 130 7 (d, 3 J CF =8 0 Hz), 130 6, 127 6, 124 2 (q, 1 J CF =287 6 Hz), 115 2 (d, 2 J C =21 0 Hz), 110 8, 104 2, 75 1 (q, 'J CF =28 6 Hz), 52 8, 41 8, 33 8, 33 0 Example 76 1 -/2-(4-Tπfluoromethylphenyl)ethyl/-2-methyl-6,7-methylene- dιoxy-3,4-dιhydroιsoquιnohnιum bromide 6 g (0 0125 moles) of 1-/2-(4-trιfluoromethylphenyl)ethyl/-2- methyl-6,7-methylene-dιoxy-3,4-dιhydroιsoquιnohne are reacted with N-bromosuccinimide in dichloromethane at 0 °C The reaction mixture is stirred for one hour at room temperature, then allowed to stand for 24 hours, and evaporated To the residue, diethyl ether is added, the precipitated crystals are filtered, recrystalhzed from a mixture of hexane and acetonitnle Thus, 1 5 g (30 %) of the title compound are obtained M p 244-245 °C Analysis for C 20 Hι 9 BrF 3 NO 2 (392 27) calculated C 54 31 %, H 4 33 %, Br 18 70 %, N 3 17 %, found C 53 65 %, H 4 35 %, Br 18 21 %, N 3 28 % 1 H-NMR (DMSO-d 6 , 200 MHz) δ 7 67 (1 H, s), 7 64 (2H, d, J=8 Hz), 7 54 (2H, d, J=8 Hz), 7 1 1 (11 H, s), 6 21 (2H, s), 3 95 (2H, t, J=8 Hz), 3 69 (3H, s), 3 49 (2H, t, J=8 Hz), 2 96 (4H, m) Example 77 1-(2-Phenylethyl)-2-methyl-6,7-methylenedιoxy-3,4-dιl)ydro- isoquinohnium iodide 3 2 g (0 011 moles) of 1 -(2-phenylethyl)-6,7-methylenedιoxy- 3,4-dιhydroιsoquιnolιne are dissolved in 30 cm 3 of acetone To the solution formed, 4 cm 3 of methyl iodide are added, and the reaction mixture is allowed to stand at room temperature during a night The precipitated yellow crystalline matter is filtered, washed with some cold acetone, then recrystalhzed from acetone Thus, 3 5 g (76 %) of the title compound are obtained M p 180 °C Analysis for C 19 H 20 INO 2 (431 28) calculated N 3 32 % found N 3 25 % 1 H-NMR (DMSO-d 6 , 200 MHz) δ. 7.69 (1 H, s), 7 28 (5H, m), 7.11 (1 H, s), 6 23 (2H, s), 3 92 (2H, t, J=7 6 Hz), 3 61 (3H, s), 3.47 (2H, t, J=7 6 Hz), 2 94 (4H, m). Example 78 1-(4-Trιfluoromethylstyryl)-2-methyl-4-propyl-6,7-methylene- dioxy-3,4-dιhydroιsoquιnolιnιum iodide dihydrate 7.2 g (0 019 moles) of 1 -(4-tπfluoromethylstyryl)-4-propyl-6,7- methylene-dιoxy-3,4-dιhydroιsoquιnolιne are dissolved in 150 cm 3 of acetone To the solution formed, 10 cm 3 of methyl iodide are poured, and the reaction mixture is allowed to stand at room temperature for a night Then the mixture is evaporated to dryness, and the oily product is crystallized from a mixture of diisopropyl ether and diethyl ether The crystalline crude product is dissolved in 90 cm 3 of acetone, precipitated by the addition of 300 cm 3 of diisopropyl ether, and filtered. Thus, 1.7 g (16 %) of the title compound are obtained. M.p.- 203-205 °C. Analysis for C 23 H 23 F 3 IN0 2 (565 38) calculated- C 48 86 %, H 4 81 %, N 2.48 %, found. C 49 08 %, H 4 73 %, N 2 63 % 1 H-NMR (DMSO-de, 200 MHz) δ 7 94 (2H, d, J=8 1 Hz), 7.84 (1 H, d, J=16 5 Hz), 7 72 (2H, d, J=8 1 Hz), 7 25 (1 H, d, J=16.5 , Hz), 7.18 (1 H, s), 6 85 (1 H, s), 6 15 (2H, s), 4.40 (1 H, dd, Jι=4.8 Hz, J 2 =14 7 Hz), 4 02 (3H, s), 3 90 (1 H, dd, ^=4.0 Hz, J 2 =14.7 Hz), 3.10 (1 H, m), 1 58 (2H, m), 1 44 (2H, m), 0.98 (3H, t, J=7.0 Hz). Example 79 1 -/2-(4-Tπfluoromethylphenyl)ethyl-2-methyl-7-chloro-3,4- dihydroisoquinohnium iodide 1 7 g (0 005 moles) of 1 -/2-(4-tπfluoromethylρhenyl)ethyl-7- chloro-3,4-dιhydroιsoquιnohne are dissolved in 30 cm 3 of acetone To the solution formed, 3 cm 3 of methyl iodide are added, and the reaction mixture is allowed to stand at room temperature for 24 hours The mixture is cooled to 0 °C, filtered, and washed with cold acetone Thus, 1 5 g (62 %) of the title compound are obtained M p 224-227 °C Analysis for C 19 Hι 8 CIF 3 IN (479 71 ) calculated C 47 57 %, H 3 78 %, Cl 7 93 %, N 2 92 %, found C 47 26 %, H 3 75 %, Cl 7 11 %, N 2 93 % 1 H-NMR (DMSO-d 6 , 400 MHz) δ 8 02 (1 H, d, J=2 2 Hz), 7 75 (1 H, dd, Jι=2 2 Hz, J 2 =8 1 Hz), 7 60 (2H, d, J=8 2 Hz), 7 52 (2H, d, J=8 2 Hz), 7 48 (1 H, d, J=8 1 Hz), 4 06 (2H, t, J=7 6 Hz), 3 81 (3H, s), 3 65 (2H, t, J=7 8 Hz), 3 1 1 (2H, t, J=7 6 Hz), 3 06 (2H, t, J=7 8 Hz) Example 80 1 -/2-(4-Fluorophenyl)ethyl/-2-methyl-6,7-ethylenedιoxy-3,4- dihydroisoquinohnium bromide 8 85 g (27 mmoles) of 1 -/2-(4-fluorophenyl)ethyl/-2-methyl-6,7- ethylenedιoxy-3,4-dιhydroιsoquιnohne are dissolved in 200 cm 3 of dichloromethane To the solution formed, 5 34 g (30 mmoles) of N-bromosuccinimide are added at 0 °C The reaction mixture is stirred at room temperature for 3 hours, then concentrated to the half of the original volume under reduced pressure From the residue, the crude product is precipitated by the addition of cyclohexane, and recrystalhzed from 20 cm 3 of isopropanol Thus, 4 23 g (38 %) of the title compound are obtained M p 177-180 °C Analysis for C 20 H 2 ιBrFNO 2 (406 30) calculated N 3 45 %, found N 3 29 % 1 H-NMR (DMSO-de 200 MHz) δ 7 61 (1 H, s), 7 31 (2H, m), 7 11 (2H, m), 6 99 (1 H s), 4 35 (4H, m), 3 95 (2H, t, J=7 4 Hz), 3 66 (3H, s), 3 47 (2H, t, J=7 6 Hz), 2 94 (4H, m) Example 81 1 -/2-(4-Trιfluoromethylphenyl)ethyl/-2-methyl-6-methoxy-7- hydroxy-3,4-dιhydroιsoquιnolιnιum iodide 2 0 g (6 mmoles) of 1 -/2-(4-trιfluoromethylphenyl)ethyl/-6- methoxy-7-hydroxy-3,4-dιhydroιsoquιnohne are dissolved in 30 cm 3 of acetone, and to the solution formed, 5 cm 3 of methyl iodide are added The precipitated crystals are filtered, washed with cold ether, dissolved in 350 cm 3 of acetone, and precipitated by the addition of ether Thus, 1 87 g (63 ) of the title compound are obtained M p 210-213 °C Analysis for C 20 H 2 ιF 3 INO 2 (491 29) calculated C 48 90 %, H 4 31 %, N 2 85 %, found C 48 56 %, H 4 42 %, N 2 96 % 1 H-NMR (DMSO-d 6 , 400 MHz) δ 9 55 (1 H, bs), 7 67 (2H, d, J=8 0 Hz), 7 56 (2H, d, J=8 0 Hz), 7 40 (1 H, s), 7 09 (1 H, s), 3 97 (2H, t, J=7 6 Hz), 3 92 (3H, s), 3 69 (3H, s), 3 41 (2H, t, J=8 0 Hz), 3 02 (4H, t J=8 0 Hz) Example 82 1 -/2-(4-Trιfluoromethylphenyl)ethyl/-2-methyl-4-propyl-6,7- ethylenedιoxy-3,4-dιhydroιsoquιnohnιum iodide 4 0 g (0 01 moles) of 1 -/2-(4-tπfluoromethylpheπyl)ethyl/-4- propyl-6,7-ethylenedιoxy-3 4-dιhydroιsoquιnohne are dissolved in 80 cm 3 of acetone After the addition of 9 g of methyl iodide, the reaction mixture is allowed to stand at room temperature for 24 hours The precipitated quaternary salt is filtered and recrystalhzed from acetone Thus, 3 1 g (56 %) of the title compound are obtained M p 177-180 °C Analysis for C 24 H 27 F 3 IN0 2 (545 38) calculated C 52 86 %, H 4 99 %, N 2 57 %, found C 52 73 %, H 5 04 %, N 2 62 % 1 H-NMR (CDCI 3 , 400 MHz) δ 7 55 (2H, d, J=8 1 Hz), 7 34 (2H, d, J=8 1 Hz), 7 29 (1 H s), 6 77 (1 H, s), 4 38 (2H, m), 4 34 (1 H, dd, Jι=5 4 Hz, J 2 =14 1 Hz), 4 29 (2H, m), 3 83 (3H, s), 3 74 (1 H, dd, Jι=4 8 Hz, J 2 =14 4 Hz), 3 64 (2H, m), 3 22 (1 H, m), 3 13 (1 H, m), 3 01 (1 H, m), 1 5-1 2 (4H, m), 0 95 (3H, t, J=7 1 Hz) Example 83 1 -/2-(4-Trιfluoromethylphenyl)ethyl/-2-methyl-6,7- ethylenedιoxy-3,4-dιhydroιsoquιnolinιum iodide 2.8 g (0 0075 moles) of 1 -/2-(4-trιfluoromethylphenyl)ethyl/-6,7- ethylenedιoxy-3,4-dιhydroιsoquιnohne are dissolved in 120 cm 3 of acetone To the solution formed, 5 cm 3 of methyl iodide are added The reaction mixture is heated under reflux for 1 hour, then cooled with ice water to 0-5 °C and stirred at this temperature for 2 to 3 hours After crystallization, the crystals are filtered, washed with cold acetone, and recrystalhzed from acetone Thus, 2 2 g (58 %) of the title compound are obtained M p 205-207 °C Analysis for C 2 ιH 2 ιF 3 IN0 2 (503 30) calculated C 50 12 %, H 4 21 %, N 2 78 %, found C 49 61 %, H 4 25 %, N 2 82 % H-NMR (DMSO-de, 200 MHz) δ 7 64 (2H, d, J=8 3 Hz), 7 58 (1 H, s), 7 52 (2H, d, J=8 3 Hz), 6 96 (1 H, s), 4 33 (2H, m), 3.95 (2H, t, J=7 5 Hz), 3 69 (3H, s), 3 49 (2H, t, J=7 7 Hz), 2.99 (4H, m) Example 84 1 -/2-(4-Fluorophenyl)ethyl/-2-methyl-6,7-methylenedioxy-3,4- dihydroisoquinohnium bromide 2.9 g (9 mmoles) of 1 -/2-(4-fluoroρhenyl)ethyl/-2-methyl-6,7- methylenedιoxy-3,4-dιhydroιsoquιnohne are dissolved in 70 cm 3 of dichloroethane, and to the solution formed, 1 7 g (0.01 moles) of N-bromosuccinimide are added under stirring The reaction mixture is stirred at 0 °C for 3 hours, then evaporated under reduced pressure To the oily residue, ether is added, the mixture is stirred at 0 °C, and the precipitated crystals are filtered Thus, 1 9 g (53 %) of the title compound are obtained M p 191 -193 °C Analysis for Cι 9 Hι 9 BrFN0 2 (392 27) calculated C 58 18 %, H 4 88 %, Br 20 37 %, N 3 57 %, found C 57 94 %, H 5 13 %, Br 20 59 %, N 3 69 % 1 H-NMR (DMSO-d 6 , 400 MHz) δ 7 68 (1 H, s), 7 31 (2H, m), 7 11 (2H, m), 7 11 (1 H, s), 6 22 (2H, s), 3 93 (2H, t, J=7 7 Hz), 3 64 (3H, s), 3 46 (2H t, J=7 7 Hz), 2 98 (2H, t, J=7 7 Hz), 2 91 (2H, t, J=7 7 Hz) Example 85 1-(4-Fluorostyryl)-2-methyl-6,7-methylenedιoxy-3,4-dιhydro- isoquinohnium bromide To a solution of 4 39 g (0 0125 moles) of 1 -(4-fluorostyryl)-2- methyl-6,7-methylenedιoxy-1 ,2,3,4-tetrahydroιsoquιnolιne in 100 cm 3 of dichloromethane, 4 6 g (0 025 moles) of N- bromosuccinimide are added at O C C, and the reaction mixture is stirred at room temperature for 3 hours Then the mixture is evaporated to dryness under reduced pressure, and, to the residue, acetonitnle is added The crystalline matter is filtered and recrystalhzed from acetonitnle Thus, 3 1 g (63 %) of the title compound are obtained M p 215-218 °C Analysis for Cι 9 Hι 7 BrFN0 2 (390 27) calculated C 58 48 %, H 4 39 %, Br 20 48 %, N 4 39 %, found C 57 70 %, H 4 36 %, Br 20 12 %, N 4 60 % 1 H-NMR (CDCI 3 , 250 MHz) δ 7 8-7 9 (2H, m), 7 65 (1 H, d, J=16 3 Hz), 7 18 (1 H, d, J=16 3 Hz), 7 08-7 15 (3H, m), 6 88 (1 H, s), 6 13 (21-1, s), 4 14 (2H, t, J=7 5 Hz), 4 07 (3H, s), 3 25 (2H, t, J=7 5 Hz) Example 86 1-(4-Trιfluoromethylstyryl)-2-methyl-6,7-methylenedιoxy-3,4- dihydroisoquinohnium bromide 4 8 g (0 0135 moles) of 1 -(4-trιfluoromethylstyryl)-2-methyl-6,7- methylenedιoxy-3,4-dιhydroιsoquιnohne are dissolved in 100 cm 3 of dichloromethane To the solution cooled to 0 °C, 2 5 g (0 0141 moles) of N-bromosuccinimide are added under stirring The reaction mixture is stirred at 0 °C for 1 hour, and at room temperature for further 2 hours The precipitated crystals are filtered and washed with some dichloromethane The crude product is recrystalhzed from a mixture (1 1 ) of ether and ethanol Thus, 2 4 g (41 %) of the title compound are obtained M p 213 °C Analysis for C 20 Hι 7 BrF 3 NO 3 (440 26) calculated C 54 56 % H 3 39 %, Br 17 76 %, N 3 18 %, found C 54 20 %, H 4 00 %, Br 17 70 %, N 3 11 % H-NMR (CDCI 3 , 250 MHz) δ 7 95 (2H, d, J=8 2 Hz), 7 83 (1 H, d, J=16 4 Hz), 7 69 (2H, d, J=8 2 Hz), 7 23 (1 H, d, J=16 4 Hz), 7 11 (1 H, s), 6 87 (1 H s), 6 13 (2H, s), 4 22 (2H, t, J=7 5 Hz), 4 08 (3H, s), 3 27 (2H, t, J=7 5 Hz) Example 87 1 -/2-(4-Fluorophenyl)ethyl/-2-methyl-6,7-methylenedιoxy-3,4- dihydroisoquinohnium iodide 3 12 g (0 01 moles) of 1 -/2-(4-fluorophenyl)ethyl/-6,7- methylenedιoxy-3,4-dιhydroιsoquιnohne are dissolved in 30 cm 3 of nitromethane To the solution formed, 7 76 g of methyl iodide are added, and the reaction mixture is stirred at 120 °C for 4 hours, then cooled to room temperature, and 50 cm 3 of ether are added to precipitate the product The crystals are filtered, washed with ether, and recrystalhzed from acetone Thus, 3 6 g (82 %) of the title compound are obtained M p 197-198 °C Analysis for Cι 9 Hι 9 FIN0 2 (439 272) calculated C 51 95 % H 4 36 %, N 3 19 %, found C 51 66 %, H 4 32 %, N 3 09 % 1 H-NMR (DMSO-d 6 , 400 MHz) δ 7 68 (1 H, s), 7 32 (2H, m), 7 12 (2H, m), 7 1 1 (1 H, s), 6 23 (2H, s), 3 94 (2H, t, J=7 7 Hz), 3 64 (3H, s) 3 46 (2H, t, J=7 8 Hz), 3 00 (2H, t, J=7 8 Hz), 2 91 (2H, t, J=7 8 Hz)

Claims: Claims 1 An isoquinohne derivative of the formula wherein Ri, R 2 and R 3 represent, independently, a hydrogen atom, a halo atom, a hydroxy group or a Cι -4 alkoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom, a Cι -4 alkoxy group or a tnfluoromethyl group R 7 means a hydrogen atom or a Cι -4 alkyl group, R 8 is a hydrogen atom or a Cι- 4 alkyl group, Rs, Re, R9 represent, independently, a hydrogen atom, or R 5 forms with R 6 a valence bond, and simultaneously R 8 forms with R 9 a valence bond, R 10 and Rn represent, independently, a hydrogen atom, a halo atom, a πitro group, a Cι_ alkoxy group, a tnfluoromethyl group or a cyano group, Xi and X 2 mean, independently, a hydrogen atom, or X T forms with X 2 a valence bond, furthermore a pharmaceutically suitable acid addition salt thereof and a quaternary derivative of the formula wherein Ri, 2, R3, R 4 , R5, Rε, R7, Re, 9, R10, R11, Xi and X 2 are as defined above, R's stands for a Cι -4 alkyl group, and A represents a residue of an inorganic or organic acid of the formula HA, or, in formula I, Ri and R 2 are as stated above, R 3 , R 6 and R 7 represent, independently, a hydrogen atom, R 8 forms with R 9 a valence bond, R 4 stands for a hydrogen atom, a C1-4 alkoxy group or a d-β alkyl group, R 5 means a hidrogen atom or a tnfluoromethyl group, R 10 and Rn represent, independently, a hydrogen atom, a halo atom, a nitro group, a Cι- alkoxy group or a tnfluoromethyl group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, furthermore a pharmaceutically suitable acid addition salt thereof, or, in formula I", Ri and R 2 are as stated above R3, R5, Re and R 7 represent, independently, a hydrogen atom, R 8 forms with R 9 a valence bond, R stands for a hydrogen atom or a Cι- 6 alkyl group, R 10 and Rn represent, independently, a hydrogen atom, a halo atom, a Cι- 4 alkoxy group or a tnfluoromethyl gro,up, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond R's represents a Cι -4 alkyl group, and A represents a residue of an inorganic or organic acid of the formula HA 2 A 1 ,2,3,4-tetrahydroιsoquιnohne derivative of the formula la as claimed in Claim 1 , wherein Ri, R 2 and R 3 represent, independently, a hydrogen atom, a halo atom, a hydroxy group or a Cι. 4 alkoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom or a Cι -4 alkoxy group, R 7 means a hydrogen atom or a Cι -4 alkyl group, R 8 is a hydrogen atom or a C 1-4 alkyl group, R 10 and Rn represent, independently, a hydrogen atom, a halo atom, a Cι -4 alkoxy group or a tnfluoromethyl group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, furthermore a pharmaceutically suitable acid addition salt thereof and a quaternary derivative of the formula wherein Ri, R2, R3, R 4 , R5, e, R7, Re, Θ, R10, R11, Xi and X 2 are as defined above, R's stands for a C 1- alkyl group, and A represents a residue of an inorganic or organic acid of the formula HA 3 A 1 ,2,3,4-tetrahydroιsoquιnohne derivative of the formula la as claimed in Claim 2, wherein Ri and R 2 represent, independently, a methoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 3 stands for a hydrogen atom, R 4 means a hydrogen atom, R 7 is a hydrogen atom, R 8 represents a hydrogen atom or a methyl group, R 10 stands for a halo atom, a tnfluoromethyl group or a methoxy group, Rn means a hydrogen atom or a methoxy group, Xi and X 2 mean, independently, a hydrogen atom or Xi forms with X 2 a valence bond, furthermore a pharmaceutically suitable acid addition salt thereof and a quaternary derivative of the formula I'a, wherein Ri, R 2 , 3, R 4 , R5, e, R7, e, R9, R10, 111 Xi and X 2 are as defined above, R's stands for a methyl group, and A represents a hahde ion 4 An isoquinohne derivative of the formula as claimed in Claim 1 , wherein Ri, R 2 and R 3 represent, independently, a hydrogen atom, a halo atom, a hydroxy group or a Cι- alkoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom a Cι- alkoxy group or a tnfluoromethyl group, R 7 means a hydrogen atom or a Cι -4 alkyl group, R1 0 and Rn represent, independently, a hydrogen atom, a halo atom, a nitro group, a Ci 4 alkoxy group, a tnfluoromethyl group or a cyano group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, furthermore a pharmaceutically suitable acid addition salt thereof and a quaternary derivative of the formula wherein Ri, R2, R3, R , R7, R10, R11, Xi and X 2 are as defined above, R's stands for a Cι -4 alkyl group, and A represents a residue of an inorganic or organic acid of the formula HA 5 An isoquinohne derivative of the formula lb as claimed in Claim 4, wherein Ri, R 2 and R 3 represent, independently, a hydrogen atom or a methoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom, a Cι -4 alkoxy group or a tnfluoromethyl group, R 7 means a hydrogen atom or a methyl group, R 10 represent a hydrogen atom, a halo atom, a nitro group, a methoxy group, a tnfluoromethyl group or a cyano group, Rn is a hydrogen atom or a methoxy group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, furthermore a pharmaceutically suitable acid addition salt thereof and a quaternary derivative of the formula I'b, wherein Ri, R 2 , R3, R 4 , R7, R10, R11, Xi and X 2 are as defined above, R's stands for a methyl group, and A represents a hahde ion 6 A 3,4-dιhydroιsoquιnohne derivative of the formula as claimed in Claim 1 , wherein Ri and R 2 represent, independently, a hydrogen atom, a halo atom, a hydroxy group or a Cι -4 alkoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom, a C1-4 alkoxy group or a Cι -6 alkyl group R 5 means a hydrogen atom or a tnfluoromethyl group, R 10 and Rn represent, independently, a hydrogen atom, a halo atom, a nitro group, a Cι. 4 alkoxy group or a tnfluoromethyl group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, furthermore a pharmaceutically suitable acid addition salt thereof 7 A 3,4-dιhydroιsoquιnolιne derivative of the formula XIV as claimed in Claim 6, wherein Ri and R represent, independently, a hydrogen atom, a chloro atom, a hydroxy group or a methoxy group, or , Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R stands for a hydrogen atom or a Cι -6 alkyl group, R 5 means a hydrogen atom, Rio and Rn represent, independently, a hydrogen atom, a fluoro atom, a methoxy group or a tnfluoromethyl group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, furthermore a pharmaceutically suitable acid addition salt thereof 8 A 3,4-dιhydroιsoquιnohne derivative of the formula XIV as claimed in Claim 7, wherein R T forms with R 2 a methylenedioxy group, R 4 stands for a Cι- 6 alkyl group, R 5 means a hydrogen atom or a tnfluoromethyl group, R 10 and Rn represent, independently, a hydrogen atom, a methoxy group or a tnfluoromethyl group, Xi forms with X 2 a valence bond, furthermore a pharmaceutically suitable acid addition salt thereof 9 A 3,4-dιhydroιsoquιnolιnιum derivative of the formula as claimed in Claim 1 , wherein Ri and R 2 represent, independently, a hydrogen atom, a halo atom, a hydroxy group or a Cι -4 alkoxy group, or Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom or a Cι -6 alkyl group R's means a Cι- 4 alkyl group, R-io and Rn represent, independently, a hydrogen atom, a halo atom, a Cι- alkoxy group or a tnfluoromethyl group, X 1 and X 2 mean, independently, a hydrogen atom, or X 1 forms with X 2 a valence bond, A represents a residue of an inorganic or organic acid of the formula HA 10 A 3,4-dιhydroιsoquιnohnιum derivative of the formula XI as claimed in Claim 9, wherein R 1 and R 2 represent, independently, a hydroxy group, a chloro atom or a methoxy group, or R ! forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom or a Cι -3 alkyl group, R's means a methyl group, Rio and Rn represent, independently, a hydrogen atom, a halo atom or a tnfluoromethyl group, Xi and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, A represents a residue of an inorganic acid of the formula HA 11 A 3,4-dιhydroιsoquιnohnιum derivative of the formula XI as claimed in Claim 10, wherein Ri forms with R 2 a methylenedioxy group or an ethylenedioxy group, R 4 stands for a hydrogen atom or a Cι -3 alkyl group, R's means a methyl group R 10 and R represent, independently, a hydrogen atom, a fluoro atom or a tnfluoromethyl group, and X 2 mean, independently, a hydrogen atom, or Xi forms with X 2 a valence bond, A represents a bromide ion or a iodide ion. 12 A process for the preparation of an isoquinohne derivative of the formula I, wherein Ri, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , Rι 0 , Rn, Xi and X 2 are as defined in Claim 1 , or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I', wherein R 1 t R 2 , R 3 , R 4 , R 5 , R 6 , R7, Rs, R9, R10, Rn, Xi and X 2 are as stated above, R' 8 and A are as defined in Claim 1 , characterized by a) for the preparation of an isoquinohne derivative of the formula lb, wherein Ri R 2 , R 3 , R 4 , R 7 , R10 and Rn are as defined in connection with formula I, X forms with X 2 a valence bond, condensing a 1 -methyhsoquιnolιne of the formula wherein R 1 ( R 2 , R 3 , R and R 7 are as stated above, with an aldehyde of the formula wherein R 10 and Rn are as defined in connection with formula I; or b) for the preparation of an isoquinohne derivative of the formula lb, wherein Ri, R 2 , R 3 , R 4 , R7, R10 Rn, Xi and X 2 are as defined in connection with formula I, subjecting a 3,4- dihydroisoquinohne derivative of the formula wherein Ri, R 2 , R 3 , R 4 , R 7 , R 10 Rn, Xi and X 2 are as stated above, R 3 stands for a hydrogen atom, to catalytical dehydrogenation, or c) for the preparation of a 1 ,2,3,4-tetrahydroιsoquιnohne derivative of the formula la, wherein Ri, R 2 , R 3 , R 4 , R 7 , R10 Rn, X 1 and X 2 are as defined in connection with formula I, R 8 represents a hydrogen atom, hydrogenizing a 3,4- dihydroisoquinolme derivative of the formula IV, wherein Ri, R 2 , R 3 , R 4 , R 7 , R10 R11, Xi and X 2 are as stated above, R 13 stands for a hydrogen atom or d) for the preparation of a 1 ,2,3,4-tetrahydroιsoquιnohne derivative of the formula la, wherein Ri, R 2 , R 3 , R , R 7 , Rio Rn, Xi and X 2 are as defined in connection with formula I, R 8 represents a Cι- alkyl group, reacting a 3,4-dιhydro- isoquinohmum derivative of the formula wherein R 1 ( R 2 , R 3 , R 4 , R 7 , R 10 Rn, Xi and X 2 are as stated above, R 12 stands for a Ci 4 alkyl group, A is as defined in connection with formula I', with a reducing agent, or e) for the preparation of an isoquinohne derivative of the formula lb, wherein Ri, R 2 , R 3 , R 7 , Rio Rn, Xi and X 2 are as defined in connection with formula I, R 4 stands for a tnfluoromethyl group, reacting a 3,4-dιhydroιsoquιnolιne derivative of the formula IV, wherein R-j, R 2 , R 3 , R 4 , R 7 , Rio, Rn, Xi and X 2 are as stated above, R 13 represents a Cι -4 alkoxy group, with an alkali metal hydroxide, or f) for the preparation of an isoquinohne derivative of the formula lb, wherein Ri, R 2 , R 3 , R 7 , Rι 0 and R are as defined in connection with formula I, R 4 stands for a tnfluoromethyl group, X ! forms with X 2 a valence bond, reacting a 1 -methyl-3,4- dihydroisoquinoline of the formula wherein Ri, R 2 , R 3 , R 4 and R 7 are as stated above, R 13 stands for a Cι -4 alkyl group, with an aldehyde of the formula III, wherein Rι 0 and Rn are as stated above, in the presence of a condensing agent, or g) for the preparation of a 3,4-dιhydroιsoquιnohne derivative of the formula XIV, wherein Ri, R 2 , R 4 , R 5 , Rι 0 , Rn, Xi and X 2 are as defined in connection with formula I, cychzing an acid amide of the formula wherein Ri, R 2 , R 4 , Rι 0 , Rn, Xi and X 2 are as stated above, R 3 stands for a hydrogen atom, and R 3 represents a hydrogen atom or a tnfluoromethyl group; or h) for the preparation of a 3,4-dιhydroιsoquinolinium derivative of the formula XI, wherein Ri, R 2 , R 4 , R' 8 , R 1 0, Rn, Xi and X 2 are as defined in connection with formula I, A represents a residue of an inorganic acid of the formula HA, reacting a 3,4- dihydroisoquinohne derivative of the formula wherein Ri, R 2 , R 4 , Rι 0 , Rn, Xi and X 2 are as defined above, with a reagent of the formula R' 8 -A, wherein R' 8 and A are as stated above, or i) for the preparation of a 3,4-dιhydroιsoquinolinium derivative of the formula XI, wherein R R 2 , R 4 , R' 8 , Rio, Rn, Xi and X 2 are as defined in connection with formula I, A represents a residue of an inorganic acid of the formula HA, reacting a 1 ,2,3,4- tetrahydroisoquinohnium derivative of the formula wherein Ri, R 2 , R 4 , R's, R10, Rn, Xi and X 2 are as stated above, with an oxidizing agent, and, if desired, converting an obtained compound of the formula I, wherein Ri, R 2 , Rs, R 4 , R5, Re, R7, s 9, R10 and Rn, are as defined in connection with formula I, Xi forms with X 2 a valence bond, to a corresponding compound of the formula I, wherein Xi and X 2 represent a hydrogen atom, by catalytical hydrogenation, or converting an obtained 1 ,2,3,4-tetrahydroιsoquιnohne derivative of the formula la wherein Ri, R 2 , R 3 , R 4 , R 7 , R 10 , Rn, X 1 and X 2 are as defined in connection with formula I, R 8 stands for a hydrogen atom, to a compound of the formula la, wherein _ R 8 represents a Cι -4 alkyl group, by reaction with a Cι -4 alkyl hahde, or converting an obtained compound of the formula I to a pharmaceutically suitable acid addition salt or liberating the base from the salt, or converting an obtained compound of the formula I to a quaternary derivative of the formula I', wherein R^ R 2 , R 3 , R 4 , Rs, Re, R7, Rs, R9, R10, R11, Xi and X 2 are as defined in connection with formula I, R' 8 represents a C1-4 alkyl group, A stands for a residue of an inorganic or organic acid of the formula HA, by reaction with a compound of the formula R's-A, wherein R' 8 and A are as stated above, or converting an obtained quaternary isoquinohne derivative of the formula I'b, wherein Ri, R 2 , R 3 , R 4 , R 7 , R10, Rn, Xi and X 2 are as defined in connection with formula I, R' 8 stands for a Cι- alkyl group, A represents a residue of an inorganic or organic acid of the formula HA, to a compound of the formula la, wherein Ri, R 2 , R 3 , R 4 , R , R10, Rn, Xi and X 2 are as stated above, R 8 stands for a Cι. 4 alkyl group, by reaction with a reducing agent 13 A pharmaceutical composition comprising an isoquinohne derivative of the formula I, wherein Ri, R 2 , R 3 , R 4 , R 5 , Re, R7, Rs, R9, R10, R11, Xi and X 2 are as defined in Claim 1 , or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I', wherein Ri, R 2 , R 3 , R , R5, Re, R7, Rs, R9, R10, R11, Xi and X 2 are as stated above, R' 8 and A are as defined in Claim 1 , as the active ingredient and one or more conventional carner(s) 14 A pharmaceutical composition as claimed in Claim 13 comprising a 1 ,2,3,4-tetrahydroιsoquιnohne derivative of the formula la, wherein R R 2 , R 3 , R 4 , R 7 , R 8 , Rio, Rn, Xi and X 2 are as defined in Claim 2, or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I', wherein Ri, R 2 , R 3 , R 4 , R7, Rs, R10, Rn, Xi and X 2 are as stated above, R' 8 and A are as defined in Claim 2, as the active ingredient 15 A pharmaceutical composition as claimed in Claim 13 comprising an isoquinohne derivative of the formula lb, wherein Ri, R 2 , R 3 , R 4 , R 7 , R10, R11, Xi and X 2 are as defined in Claim 4, or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I'b, wherein R^ R 2 , R 3 , R 4 , R7, R10, R11, Xi and X 2 are as stated above, R' 8 and A are as defined in Claim 4 as the active ingredient 16 A pharmaceutical composition as claimed in Claim 13 comprising a 3 4-dιhydroιsoquιnohne derivative of the formula XIV, wherein Ri, R 2l R 4 , R 5 , R 10l Rn, Xi and X 2 are as defined in Claim 6 or a pharmaceutically suitable acid addition salt thereof as the active ingredient 17 A pharmaceutical composition as claimed in Claim 13 comprising a 3,4-dιhydroιsoquιnohnιum compound of the formula XI, wherein R 1 τ R 2 , R 4 , R' 8 , R1 0 , Rn, Xi, X 2 and A are as defined in Claim 9, as the active ingredient 18 A method of treatment in which a patient suffering from especially a disease of the central nervous system is treated with a non-toxic dose of an isoquinohne derivative of the formula I, wherein Ri, R 2 , R 3 , R 4 , R 5 , Re, R7, Rs, R9, R10, Rn, Xi and X 2 are as defined in Claim 1 , or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I', wherein R-,, R 2 , R 3 , R 4 , R 5 , R 6 , R7, Rs, R9, R10, Rn, Xi and X 2 are as stated above, R' 8 and A are as defined in Claim 1 19 A process for the preparation of a pharmaceutical composition having especially anxiolytic effect, in which an isoquinohne derivative of the formula I, wherein Ri. R 2 , R 3l R 4 , R5, Re, R7, Rs, R9, R10, R11, Xi and X 2 are as defined in Claim 1 , or a pharmaceutically suitable acid addition salt thereof or a quaternary derivative of the formula I', wherein R^ R 2 , R 3 , R 4 , R5, Re, R7, Rs, Rg, R10, R11, Xi and X 2 are as stated above, R' 8 and A are as defined in Claim 1 , is converted to a pharmaceutical composition using one or more conventional carner(s)

Inventors: BALAZS LASZLO, BARKOCZY JOZSEF, BILKEI-GORZO ANDRAS, DOERNYEI GABOR, DOMAN IMRE, EGYED ANDRAS, GACSALYI ISTVAN, GREFF ZOLTAN, INCZE MARIA, KOTAY-NAGY PETER, LEVAY GYOERGY, POSZAVACZ LASZLO, RACZNE BARNOGEL JUDIT, RATKAI ZOLTAN, SERES PETER, SIMIG GYULA, SZANTAY CSABA, TIHANYI KAROLY, BALAZS, LASZLO, BARKOCZY, JOZSEF, BILKEI-GORZO, ANDRAS, DOERNYEI, GABOR, DOMAN, IMRE, EGYED, ANDRAS, GACSALYI, ISTVAN, GREFF, ZOLTAN, INCZE, MARIA, KOTAY-NAGY, PETER, LEVAY, GYOERGY, POSZAVACZ, LASZLO, RACZNE BARNOGEL, JUDIT, RATKAI, ZOLTAN, SERES, PETER, SIMIG, GYULA, SZANTAY, CSABA, TIHANYI, KAROLY
Applicants: BALAZS LASZLO, BARKOCZY JOZSEF, BILKEI GORZO ANDRAS, DOERNYEI GABOR, DOMAN IMRE, EGYED ANDRAS, EGYT GYOGYSZERVEGYESZETI GYAR, GACSALYI ISTVAN, GREFF ZOLTAN, INCZE MARIA, KOTAY NAGY PETER, LEVAY GYOERGY, POSZAVACZ LASZLO, RACZNE BARNOGEL JUDIT, RATKAI ZOLTAN, SERES PETER, SIMIG GYULA, SZANTAY CSABA, TIHANYI KAROLY, BALAZS, LASZLO, BARKOCZY, JOZSEF, BILKEI-GORZO, ANDRAS, DOERNYEI, GABOR, DOMAN, IMRE, EGIS GYOGYSZERGYAR RT., EGYED, ANDRAS, GACSALYI, ISTVAN, GREFF, ZOLTAN, INCZE, MARIA, KOTAY-NAGY, PETER, LEVAY, GYOERGY, POSZAVACZ, LASZLO, RACZNE BARNOGEL, JUDIT, RATKAI, ZOLTAN, SERES, PETER, SIMIG, GYULA, SZANTAY, CSABA, TIHANYI, KAROLY
Application year: 2000
Main classification: C07D217
IPC codes: A61K31, A61P25, C07D217, C07D491