DE1695921A1 - Process for the preparation of 1- (2-pyridyl) -3,4-dihydro-isoquinolines - Google Patents

Description

Γ -Τ'ί'Γ. ^ Γϊίπ - D-. E,

Case 5/384
Dr.Pl./β.-

"Process for the preparation of .on l- (2-Pyria,> a.) - 3,4-dihydro-isoquinolines"

Additional registration to the additional registration T 33404 IVd / 12p to the Main registration T 28 238 IVd / 12p.

In the German federal sponsorship fc ................... (file number T 53 404 IVd / 12p, additional application to the main application T 28 238 IVdX12p) becomes / a new method of production of l- {2-pyridyl) -3,4-dihydro-isoohinolinen of the general Pocaiel I.

/ 2

109837/1533

.. V

It has now been found that l- (2-Pyriayl) -3, ^ dihydro

isoquinolines of the general formula I,

Hh A

R.

in which the leftovers

R- and Rp-, which can be identical or different, are alkyl radicals with 1-3 carbon atoms,

R, a hydrogen atom, a methyl group or a halogen atom and R and R ₅ , which can be the same or different, denote hydrogen atoms or methyl groups, and their physiologically acceptable salts with inorganic or organic acids, can also be prepared by the following processes!

By
A) Implementation of 2-cyanopyridines of the general formula

II.

in which the rest

has the meanings mentioned at the beginning, or their

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■ ■ - 3 - ■

mineral acid salts with compounds of the general Formula III,

III

in which the leftovers

R ₁ , Rp, Rz and R ₅ - have the meanings mentioned at the beginning, one of the radicals X or Y is a Wasseiöboffatom and the other is a hydroxyl group, which can optionally be esterified with carboxylic acids or sulfonic acids, or a halogen atom or in which the radicals X and -Y together represent a double bond.

B) By reacting 2-cyanopyridines of the general Formula II or their mineral acid salts with allylbenzenes of the general formula IV,

CH - C = CH -

IV

10 9 8 3 Ψί T53 3

Rp ₌ R and R ₁ - possess the above-mentioned meanings and R ₁ 'is a hydrogen atom or a lower alkyl group and R, by the relation R, the same -CHp-R ₁ is connected. ¹

C) By reacting 2-cyanopyridines of the general formula or their mineral acid salts with aryl-cyclopropanes of general formula V,

HR ₀ '

R,

in which the rest

R, has the meanings mentioned at the outset, and R-, 'and Rg' are hydrogen atoms or lower alkyl radicals, where a compound or a mixture of two compounds of the general formula I - depending on whether R-, 'is R ₂ ' or R ₁ ¹ not equal to Rp ¹ - arise in which either the radical R _{1 is} equal to R-, ¹ and R _{2 is} equal to -CH ₂ -R ₂ 'or R _{2 is} equal to R ₂ ¹ and R _{1 is} equal to -CH ₂ -R ₁ ' , and R _{5 represents} a hydrogen atom.

D) By reacting 2-cyanopyridines of the general

Formula II or their mineral acid salts with aryl-cyclopropanes of the general formula VI,

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in which the rest

R, which has the meanings mentioned at the outset, and the radicals R ₁ and R _{2 are} methyl groups ", R ^{1 represents} a hydrogen atom and is linked to R ₅ by the relationship R ₅ is -CH ₂ -R.

E) By cyclization of 2-picolinic acid amides of the general Formula VII,

HR _c

in which the leftovers

Rj, R ₂ , R-, R, and R _{5 have} the meanings mentioned at the beginning.

The compounds of the formula I prepared according to the invention can by conventional methods with inorganic or organic acids are converted into their physiologically compatible salts. The following acids come into consideration, for example: Hydrochloric acid, hydrobromic acid, sulfuric acid, tartaric acid, Maleic acid, acetic acid, citric acid.

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The methods A) to D) in the presence of acidic condensing agents, preferably at temperatures between 50 and 18O ⁰ O, advantageously in an organic Iosungsmittel | for example * toluene, benzene, xylene, chlorobenzene, o-dichlorobenzene, nitrobenzene, tetrahaloroethane, tetrachlorethylene, diphenyl ether, diethyl ether, acetic acid. Strong acids, preferably concentrated sulfuric acid, are used as acidic condensing agents. Other suitable acidic condensing agents are, for example, phosphoric acid and polyphosphoric acids, polyphosphoric acid esters, aromatic or aliphatic sulfonic acids, boron trifluoride etherate in the presence of catalytic amounts of water, zinc chloride in the presence of acetic acid and complex halogen acids such as, for example, anhydrous aluminum chloride, tin tetrachloride, antimony trachloride, antimony trachloride , Ferric chloride, zinc chloride and anhydrous hydrogen halides are generated in situ * '

In processes A) to D), either a gyanopyridine ^{w of} the formula II or its salt, for example its hydrogen sulfate, can first be admixed with the acidic condensing agent and then a compound of the formulas IH; IV, V or VI entered, ■ .or A mixture of compounds of the formula III or IV or V or VI can be presented and the acidic condensing agent added to this afterwards, or it can be added to the presented, if necessary to the required reaction temperature preheated acidic condensing agent a mixture of compounds of the general formulas-II and III or * IV or V or

VI.

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When using a complex halo acid as the acidic condensing agent, it is advisable to first prepare the corresponding nitrile metal halide complex from a cyanopyridine of the general formula II and a suitable metal halide and to prepare this without further purification with a compound of the general formulas III, IV, V or VI at temperatures between 50 and 180 ⁰ O, preferably between 100 and 170 ° 0, converted to a dihydroisoquinoline of the general formula I with the introduction of hydrogen halide.

The reaction of the cyanopyridine of the formula II with the equimolar amount of a metal halide takes place according to methods which are customary per se, for example according to that of Klages and Grill, Liebigs. Ann. Ohem. 394. , 29 (1955), described method. It is advantageous when working in the presence of a Interten solvent and at temperatures between 0 and 7O ⁰ C. The in process C, in the event that in the starting compound of the formula V R-. 'Is not equal R _2', obtained mixture of two compounds of general formula I can so unravel for example by fractional crystallization of the bases or their salts, such as their hydrochlorides, oxalates or maleates or by preparative gas chromatography by known methods.

The cyclization process E) takes place in the one for ring closures in the usual Bisehler-Napieralski manner by treating with the cyclizing agents commonly used for this purpose, e.g. phosphorus oxychloride, Zinc chloride, phosphorus pentachloride and polyphosphoric acid esters. The use of phosphorus pentoxide or a mixture of phosphorus oxychloride is particularly advantageous and phosphorous pentoxide or a mixture of phosphorus oxychloride and zinc chloride or from polyphosphoric acid. In some cases

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- 8 it is of advantage if you get the pyridinecarboxylic acid amld first

treated with phosphorus pentachloride and then with aluminum chloride.

The cyclization is expediently carried out in the presence of anhydrous, inert solvents, for example o-dichlorobenzene, toluene, xylene, tetralin, nitrobenzene _/ chloroform, and at temperatures between 25 and 250 ^° C.

1- (2-pyridyl) -3,4-dihydro-isochinoline is known from the literature (H. Irving and A. Hampton, J. Chem. Soc. London 1955t, pages 430-432). However, this compound could not be obtained in pure form in the reworking; Strong contamination of 1- (2-pyridyl) -isoquinoline and 1- (2-pyridyl) -l, 2,3,4-tetrahydroisoquinoline was always found, which could not be removed by simple means. In contrast, the 1- (2-pyridyl) -3,4-dihydro-isoquinolines obtained by the present invention is free of roportionierungsprodukten Disp.

The carbinols of the formula III used as starting materials can, as far as they are new, according to known methods, e.g. by converting the corresponding ketones, in special Cases also of the aldehydes, obtained with Grignard reagents

.the hydroxy group , become. The carbinols can be exchanged for halogen atoms in the usual way, for example by treatment with hydrogen halide, phosphorus halides and the like -phenylpropane (boiling point 86-89 ⁰ C) win in good yield.

The styrenes of the formula III, insofar as they are not known from the literature, obtainable by elimination of water from the carbinol in a conventional manner, such as ß, ß-dimethylstyrene ₂ 69-70 ⁰ C) of 2-methyl-l-phenyl-propanol ^J (2). ™ 109837/1533

Most of the allylbenzenes of the general formula IV used as starting materials are known (Christoph Rüchardi; Chem. Ber. % ±, 2606, 2622, 2623 / 196I / \ JF Bunnett, George T. Davis and Hiroshi Tanida, J. Amer. Formerly Soc . 84, 1607/1962 /; Percy Warrick, Jr. and William H. Saunders, Jr., J. Amer. Chem. Soc. 84, 4098/1966 ).

The cyclopropanes of the general formula V and VI can, as far as new, are produced according to methods known from the literature. Pyrolysis, for example, is suitable accordingly substituted 5-aryl-2-pyrazoline (Yu. S. Shabarov et al, J.Gen. Chem. USSR £ 4, 2861 - 2864 / Ϊ964 / or G. Lardelli and 0. Jeger, HeIv. Chim. Acta £ 2., 1817-1835 / Ϊ942 / or the Addition of dihalocarbenes to styrenes and subsequent dehalogenation with sodium in methanol (Wesley J. Dale and Paul E. Swartzentruber, J.Org. Chem. 24, 955 - 957 / Ϊ959 /) ·

Let the pyridinecarboxamides of the general formula VII obtained by customary methods, for example by reacting pyridine carboxylic acid chlorides or esters with the corresponding amines.

The compounds of general formula I have valuable pharmacological properties, in particular they have comparatively weak anti-inflammatory and sedative vision Properties - a considerable activating effect

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the perments of the liver, measured in routine tests by the shortening of barbiturate sleep in rats. before
Most of all, however, they are intermediate products in the manufacture of pharmaceuticals.

The following examples are intended to illustrate the invention in greater detail explain

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example 1

3,4-dihydro-g ^ -dimethyl-1-U-pyridylj-isoquinoline

500 ml of conc. Sulfuric acid, whereby it is ensured by cooling with ice water that the temperature of the mixture does not exceed ^{+ 1O 0 O.} After cooling has ceased, 150 g of 2-benzyl-2-propanol are run in, the temperature rising ^{to about TO 0 O.} Man "heated for 1 hour at 8O ⁰ G, allowed to cool, pour the mixture onto 2 kg of crushed ice and extracted twice with 200 ml ether.

The ether extracts are discarded. The aqueous phase is made ammoniacal and extracted exhaustively with ethylene chloride. The solvent is evaporated off, the remaining residue is distilled in a pein vacuum (bp q q,

^{116-117 0} O) After recrystallization from petroleum ether, white crystals with a melting point of 104-105 ⁰ G are obtained; Yield 159 δ

Similar results are obtained when using benzene, Nitrobenzene, Tetraehloräthan, Tetrachloräthylen, Ghlorbenzol, Diphenyl ether or glacial acetic acid as a solvent.

Example 2 ".

7-0hlor-3.4-dihydrO-3 * 3-dimethyl-1- (2-pyridyl) -isoquinoline

In the mixture obtained as in Example 1 of 31.2 g '2-gyanopyridine, 90 ml of o-dichlorobenzene and 300 ml of conc. Sulfuric acid is left with 55.2 g of 2- (4-chlorobenzyl) -2-propanol

shrink, whereby the temperature rises to about 50 ⁰ C. The mixture is heated to 100 - HO ⁰ G for a further 2 hours, poured onto 1 kg of ice and worked up as in Example 1. The product obtained in a yield of 20 g of a light yellow oil can be converted into its dihydric chloride by treatment with an ethereal hydrogen chloride solution. After twice recrystallization from a mixture of ethyl acetate and methanol, the colorless crystals melting at 185 ⁰ C

Example 3

3.4-Dihydro-5.3-diethyl-1- (2-pyridyl) -isoquinoline

15.6 g of 2-cyanopyridine are added dropwise with stirring _; dissolved in 30 ml of benzene, to 60 ml of conc. Sulfuric acid at a temperature of 0 ° to + 5 ⁰ C and then added with stirring 27 g of 2-ethyl-lphenyl-2-butanol at once, maintaining the temperature at 75 ° G increases. The reaction mixture is kept at this temperature for 30 minutes, then it is poured into ice and the acidic solution is extracted with benzene. The benzene solution is discarded. The acidic aqueous phase is then made ammoniacal with cooling and the oil which separates out is taken up in benzene. The benzene solution is washed several times with water, dried and freed from the solvent. The remaining residue is distilled in vacuo. 28g of the above dihydroisoquinolines obtained as a yellowish oil, bp ₀ 05 mm * ¹⁵⁸ °° its dihydrochloride echmilzt at 181 ⁰ C.

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Example 4

3,4-dihydro-3,3-dimethyl-1- (2-pyridyl) isoquinoline

Using the procedure described in Example 3 and obtained from l-phenyl-2-methyl-2-propanol, the desired compound of mp. 104 - 105 ⁰ C.

Example 5

3,4-dihydro-3-ethyl-3-methyl-1- (2-pyridyl) iso quinoline

10.4 g of 2-cyanopyridine in 20 ml of o-dichlorobenzene are added ^{with 26 g of tin tetrachloride while cooling at 0} ° C., 24.0 g of 2-chloro-2-methyl-1-phenyl-butane are added with stirring and the mixture is heated 4 hours to 130 ⁰ G * is then the solvent poured off from the solid residue triturated with this 40 $ aqueous sodium hydroxide solution and extracted with chloroform. The chloroform solution is extracted with dilute hydrochloric acid and the acidic aqueous solution is made alkaline with sodium hydroxide solution and extracted again with chloroform. The residue remaining after the solvent has been evaporated off is distilled in vacuo. 8 g of the dihydroisoquinoline of Kp _Q Qlmm ¹² ^ ~ ° ¹² ^ ° ^G

Example 6

3,4-Dihydro-3 »3-dimethyl-1- (2-pyridyl) -isoquinoline

Using the procedure described in Example 3 and obtained from 2-chloro-2-methyl-l-phenyl-propane (Kp _13rm 89-91 ⁰ C) gave the desired compound, m.p. «104-105 C,

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Example 7

3,4-Dihydro-3 ₁ 5-dimethyl-lT (2-pyridyl) -isoquinoline

The solution of 5.2 g of 2-cyanopyridine in 15 ml of anhydrous o-dichlorobenzene is added dropwise with 13.0 g of sin tetrachloride and dry hydrogen chloride gas is passed in for 5 minutes. One gives 6.6 g of (2-methyl-allyl) -benzene to, wherein the temperature of the mixture rises to 65 to 7O ⁰ C, and then heated 10 hours at 130-14 OOC. It is allowed to cool, poured onto 200 g of ice and the procedure is continued as in Example 1; This gives 2.7 g of colorless crystals of mp. 104 - 105 ⁰ C.

When using 6.65 g of aluminum chloride instead of 13.0 g Tin tetrachloride gives 2.0 g of the same compound.

Example 8 ■

3,4-dihydro-3 «3-dimethyl-1- (6-methyl-2-pyridyl) isoquinoline

5.9 g of 2-cyano-6-methyl-pyridine are added in the presence of 15 ml o-dichlorobenzene and 25 ml of conc. Sulfuric acid with 6.6 g of l-methyl-2-phenyl-cyGlopropane (mixture of 2 isomers in

approximate quantity ratio l: 2, bp _20mm 73-75 ° C, η ^ ⁰ 1.5211), as described in Example 1, implemented. 7.6 g of colorless crystals with a melting point of 77 ° C. are obtained (from petroleum ether).

Example 9

3,4-dihydro ~ 3 »3 y4-trimethyl-1- (2-pyridyl) -isoquinoline

5.2 g of 2-gyanopyridine are added in the presence of 15 ml of o-dichlorobenzene and 25 ml conc. Sulfuric acid with 7.3 g -l, l-I) imethyl-2-phenyl-

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" ¹⁵ 1635921

cyclopropane (Kp _1Omm 67-69 C η ^ 1.5050), reacted as described in Example 1. "Yield: 8.4 g of a colorless oil, bp _n" a 120-122 ⁰ G.

Example 10 3,4-I) ihydro-3,3-dimethyl-1- (2-pyridyl) -isoquinoline

12.7 g of KZ (l, l-dimethyl-2 * phenyl) -äthyl7 ~ pyridine-2-carboxamide (mp. 76 - 78 ⁰ C) in 50 ml of xylene is stirred for 8 hours at room temperature together with 20 g of phosphorus pentoxide and 4 -0 g of phosphorus oxychloride, then refluxed for 12 hours »enters the reaction product in water, separates the solvent layer, shakes the aqueous solution several times with water and discards the organic phase. The dihydroisoquinoline is separated from the acidic, aqueous solution by adding matron lye, it is taken up in chloroform, this is evaporated and the residue that remains is distilled. This gives 4.5 g of 3 '4-dihydro-3,3-dimethyl-l- (2-pyridyl} isoquinoline, bp ¹¹⁶ ° ^c _Q 03mm, mp. 104 - 105 ° C.

Example 11

3.4-Hydro-3 * 3-diethyl-1- (2-pyridyl) -i so quinoline

To 24.2 g of li - / (l, l-3) ethyl-2-phenyl) -ethyl / -pyridine-2-carboxamide (Melting point 83-84 ° C.) in 400 ml of o-dichlorobenzene is added 22.5 g of phosphorus pentachloride, stirred for one hour at room temperature, then add 22.5 g of powdered, anhydrous aluminum chloride added and heated for 90 minutes with stirring at a

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- 16 - 1625U21-

Outside temperature of 100 - 120 ⁰ C.

After cooling, it is decomposed by adding ice and water and separating the aqueous layer, which is shaken out with ether. The ether shakes are discarded. The base is freed from the aqueous solution by adding 4-0% sodium hydroxide solution, it is taken up in chloroform and, after the solvent has been driven off, it is distilled in vacuo. 8 g of a yellowish oil with a _{boiling point of 0} Ql - 13S ⁰ C, the dihydro chloride of which ^{melts at 181 0} C, is obtained.

In. same method and in about the same yield as in Example 11 described is obtained

i , 4-dihydro- ?! * 3-dimethy 1-1- (2-pyridyl) —is <äch! No.lin vom Sehmp. 104-105 ⁰ C.

from E-Zl 1,1-Dimethy 1-2-phenyl) -äthyiy-pyrldin-S-carbo-acid amide,

3,4-dihydro-3-ethyl-3-methyl-1- (2-pyrldyl) -isoquinoline

from Kp _nn , _mm 126 - 127 ⁰ C
Uf Ui mm

from N - / (l-ethyl-l-methyl-2-phenyl) -ethyl / -pyridine-2-carboxamide (bp _{0 fQ5} ^ 145 - H6 ° C),

3,4-dihydro-3 <3,4-trimethyl-1- (2-pyridyl) -isoquinoline

from Kp _{n Ί m} 128 ⁰ C
^{r 0.1} mm

from N - / (l, l, 2-Trimethy1-2-phenyl) -äthylZ-pyridine ^ -carboxylic acid-

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- .17 -

3, 4-dihydro-3> 3, 7-trimethyl ~ 1- (2-pyridyl) -isochinolin

from bp _{0 05m} 121 ° C from l- ££ - (4-methylphenyl) -l, l-dimethy: i7-ethylj -pyridine - ^ - carboxamide (bp q nc- ™ 155 ° ö)

7 ~ Glilor-3 _< 4-dihydrQ ~ 3,3-dimethyl-1- (2-pyridyl) -i3ochinoline

DihydrolDromid which melts under black coloration and decomposition at 240 ⁰ G, of H-FR2 (4-Ghlorphenyl) -l, l-ethyl dimethyl7 · | -pyridin-2-earbons.ä'u.reamid (m.p., 58-60 ° ö).

Bas dihydrochloride melts at 185 ⁰ C.

10 9-837 / 15.33

Claims (12)

Patent claims 1. Process for the preparation of new 1- (2-pyridyl) -3,4-dihydro-isoquinolines of the general formula I, according to DBP (German additional registration T 33 404 IVd / 12p on the German patent application, 2 28 238 rVd / 12p), in which the remnants R-, and Rp, "which can be the same or different, Alkyl radicals with 1-3 carbon atoms, R, - a hydrogen atom, a methyl group or a halogen atom and R * and R ₁ -I, which can be identical or different, denote hydrogen atoms or methyl groups, and their physiologically acceptable acid addition salts with inorganic or organic acids, characterized in that 109837/1533 A) 2-cyanopyridines of the general formula II, <x ^H 4 ~ P ~ I II in which the rest R., the above-mentioned meanings, or their mineral acid salts, in the presence of acid condensation agents at temperatures between 50 and 18O ⁰ C with compounds of the general formula III, I ⁵ I ¹ C - C-Y I. I. X R ₂ III in which the leftovers R ₁ , R ₂ , R, and R _{5 have} the meanings mentioned at the beginning, one of the radicals X or Y is a carbon atom and the other is a hydroxyl group, which can optionally be esterified with carboxylic acids or sulfonic acids, or a halogen atom or in which the radicals X and Y together represent a double bond, are implemented or that 10 9837/1533 '- 20 - B) 2-Cyanpyridines of the general formula II or their mineral acid salts in the presence of acidic condensing ^{agents at temperatures between 50 and 180 0} O with AlIyI-benzenes of the general formula IV, CH - C = GH - IV in dear the leftovers R «.» β · ζ and R ₁ - oils meanings mentioned at the beginning Täesitzen «and the remainder E-, ^|; a hydrogen atom or a "lower alkyl group" means: and with E ^ connected by the relationship Β- * equal -GH ^ -S-, ', adier ciaß G) 2-cyanopyridines of the general formula II. Or er = their mineral acid Salts. in the presence of acidic condensing agents at temperatures between 50) and 180 ° G with arylcyclopropanes the general formula V, S ₂ ' 10 9 8 3 7/1533 in which the rest R, which has the meanings mentioned at the outset, and R-, 'and Rp' mean hydrogen atoms or lower alkyl radicals ", are implemented, where a compound or a semicircle of two compounds of the general formula I - depending on whether R-, ^{1 is the} same Rp 'or R-, ^{1 is} not equal to Rp' - arise in which either the radical R-, equal to R ₁ 'and Rp equal to -GH ₂ -R ₂ ' or R ₂ equal to R ₃ ¹ and R ₁ equal to -OH ₂ -R _{1 is} ¹ , and R ₁ - is a hydrogen atom, or that D) 2-cyanopyridines of formula II or their mineral acid salts in the presence of acidic clay condensing agents "at temperatures between 50 and 18O ⁰ C with aryl cyclopropanes of the general formula VI, VI in which the rest R, has the meanings mentioned at the outset, and the radicals S and Rp represent methyl groups R ₅ ^{1 represents} a hydrogen atom and, with R ^ by the relationship R _{5 is} equal to -GH ₂ -Rc 'linked * have been implemented or that λ) 2-picolinic acid amides of the general formula VII ₆ 109837/1533 T62B921 ¥ 11 in which the leftovers R ₁ , R ₂ , Rz, R, and R ₁ - have the meanings mentioned at the beginning, are cyclized in the presence of dehydrating agents at temperatures between 25 and 25O ⁰ C and these compounds of the general formula I, if desired, by methods known per se in their physiologically compatible salts are converted with inorganic or organic acids. 2. The method according to claim 1, characterized in that the Reaction is carried out in a solvent. ^ 3. The method according to claim IA to 1 D and 2, characterized in that as condensation acids, Lewis acids and their complexes with hydrogen halide acids can be used. 4 «Process according to claim 1 A to 1 D and 2, characterized in that the complexes prepared from compounds of the formula II with Lewis acids without further purification with compounds of the formulas III, IV, V or VI by introducing hydrogen halide zvl compounds of Formula I are implemented. 109837/1533 5. Verfakrem according to claim 1 E and 2, characterized * that as a condensing agent phosphorus oxychloride, phosphorus pentoxide, EhosphorpentaelüLorid, phosphoric acid ester, zinc chloride or a semicircle thereof is used. 6. Author. according to claim 1 E and 2, characterized in that that Yer / Mjidliingett of the formula VII with phosphorus pentahalide reacted and then with aluminum chloride to form compounds the Foxiniel I are cyclized. 7. Ver / fataren according to claim IC, 2, 3 and 4, characterized gekennseiclmet that a resulting mixture of two compounds of the general formula I, if R ₁ ^{1 is} not equal to Rg *, is separated mach usual methods. 8. Kernel- (2-pyridyl) -3,4-dihydro-isoquinolines of the general Formula I,. in which the leftovers 109837/1533 Ή.-, and Rp, which can be the same or different, alkyl radicals with 1-3 carbon atoms,. R, a hydrogen atom, a methyl group or a halogenatora and R. and R-, which can be the same or equal to each other, are hydrogen mean atoms or methyl groups, as well as their physiologically acceptable salts with inorganic or organic Acids. 9 .. 3,3-Diethyl-3,4-dihydro-1- (2-pyridyl) -isoGhinoline and its salts. 10. 3,4-Dihydro-1- (2-pyridyl) -3,3,7-trimethyl-isoquinoline and its salts. - 11. 3,4 ~ dihydro-3,3-dimethyl-1- (2-pyridyl) -isoquinoline and its salts. 12. 3-Ethyl-3,4-dihydro-3 '~ methyl-1- (2-pyridyl) -isoquinolia and its salts. . 1/1 μ Ι