FI56532C - FRUIT PROCESSING OF A PSYCHOTROPISTIC VERKANDE 3-CARBAMOYL-1-THIAISCHROMAN-1,1-DIOXIDE DERIVATIVES - Google Patents

Description

ESFH [B] (11) ^ ANNOUNCEMENT. , LJ '} UTLÄGGNINGSSKRIFT 9 t> 9 J £ C (45) Patent nydnr.ctty 11 C2 1930

IjgVgji Patent noddolat '(51) Kv.lk.' / Int.CL * C 07 D 327/06 SUOMI - FINLAND (21) p * tenttihlkemul - Pat «u» n »öknlng 1301 / T1 * (22) Hakemiipilvl - Aniöknlngidig 29. θ4. 74 (23) Alkupilvl — Giltlghetsdag 29.04.74 (41) Become public —— Bllvit offantllg j.1 "jh

Patent and Registration Office. (44) Nlht4vUulpanon Ja kuL | uikai, Un pvm.-

Patent- och registantyralaan Ansakin utiigd och uti.tkrift «n publicsrtd 31.10.79 (32) (33) (31) Pyydatty etuolkau * —Begird prlorltet 02.05.73

The German Democratic Republic-Democratic Republic of Germany (DD) WP 170661+ (71) VEB Arzneimittelwerk Dresden, Postfach 89/90, 8122 Radebeul,

German Democratic Republic-Democratic Republic of Germany (DD) (72) Gunter Laban, Dresden, Werner Pöpel, Radebeul, Gottfried Faust,

Radebeul, Kurt Stade, Radebeul, German Democratic Republic-Democratic Republic of Germany (DD) (7 * 0 Oy Borenius & Co. Ab (5 * 0 Method for the development of new psychotropically active 3-carbamoyl-1-thia-isochroman-1,1-dioxide for the preparation of 3-carbamoyl-1-thia-isochroman-1,1-dioxide derivatives - for the preparation of psychotropic networks

The invention relates to a process for the preparation of novel 3-carbamoyl-1-thia-isochromane-1,1-dioxide derivatives of the general formula ^ CH 2 R 1 (I) CH-O 0.

3 | ^ R3 CH-O ^ NH-CH-CHO-C-NH-R5 3 '2 2' 4 ^ RZ R * 0 0 where 1 4 R ... R are identical or different and denote a hydrogen atom or a methyl group R5 denotes a straight-chain or branched alkyl group having 1 to 6 carbon atoms, a benzyl, β-phenylethyl or cyclohexyl group and their acid addition salts with physiologically acceptable inorganic or organic acids.

The process according to the invention is characterized in that the general formula 2 56532

S ^ T °

CH 3 -C 6 wherein R is as defined above and R is a halogen atom such as chlorine or bromine, or a hydroxy or alkoxy group, is reacted with the general formula R 3 H, N - CH - CHO - C - NH - R5 (III) ί t * t R2 R4 • 2 3 4.5 wherein R, R, R and R are as defined above, with the amines or their acid addition salts and the compounds of the general formula I obtained, if obtained in the form of bases, if desired converted into its acid addition salts by means of physiologically acceptable inorganic or organic acids.

The compounds according to the invention have not yet been described in the literature. However, FI patent publication 50 878 describes Ν, Ν-disubstituted 3-carbamoyl-1-thia-isochromane-1,1-dioxide derivatives which differ from the compounds of the present invention due to the tertiary N atom in the basic side chain. Compounds of general formula I have typical differences in the quality of psychotropic effects compared to the Ν, Ν-disubstituted 3-carbamoyl-1-thia-isochromane-1,1-dioxide derivatives described in the above-mentioned FI patent publication. They lack the central choline-acting phenomena detectable in small experimental animals while maintaining the central cortical effect.

The anti-reserpine-induced hypothermia effect of the compounds I according to the invention and their analgesic, muscle tension-reducing and cataleptic effects were studied. 3- (4'-Dimethylamino-4'-methylpentyl- (2 *) -carbamoyl) -6,7-dimethoxy-1-thia-isochromane-1,1-dioxide was used as a reference substance (according to the FI patent publication). 50 878 according to Example 2). The results are shown in Tables 1 ... 3.

3,56532

The psychotropic effect of Compounds I in experiments on reducing catalepsy and muscle tension in animals is considerably stronger than that of the reference compounds. Their analgesic effect is also stronger than that of the reference compound. In addition, the compounds have the opposite effect on reserpine hypothermia.

The experiments were performed as follows: 5 mg / kg reserpine (DAB 7) was administered intraperitoneally to male mice. 16 hours later, intraperitoneal dosing of the test compound also followed. Rectal temperature was measured at hourly intervals for 4 hours after injection of the compound with an electronic thermometer equipped with a thermistor. The results were compared with the control group (reserpine-NaCl) and the temperature difference was calculated.

The analgesic effect on male mice was measured by the "hot plate method" at 53 ° C. This hot plate method is a standard pharmacological method for measuring the emotional capacity of animals after administration of a test substance on a heated plate. The effect of reducing muscle tension was measured in a mouse traction test. In this case, the percentage of animals that could no longer pull themselves up on a horizontal bar was calculated. The cataleptic effect was tested with a horizontal rod on which the untreated animals spontaneously ran. The effect of the compounds was calculated as the percentage of animals that no longer ran spontaneously on the bar.

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Mention may be made of amines of the general formula III which can be prepared by known methods

1-amino-3-n-propylaminopropane (b.p. 75-77 ° C), 1-amino-3-cyclohexylaminopropane (b.p. 116 ° C), 2-methylamino-4-amino- 2-methylpentane (b.p. 58-62 °), 2-n-propylamino-4-amino-2-methylpentane (b.p. 5-8 ° C), 2-n-butylamino-4-amino -2-methylpentane · (Kp ^ 2: 88-93 ° C), 2-n-hexylamino-4-amino-2-methylpentane (KpQ 83-87 ° C), 2-isobutylamino-4 -amino-2-methylpentane (b.p. 87-89 ° C), 2-isopropylamino-4-amino-2-methylpentane (b.p.: 70-75 ° C), 2 sec. -butylamino-4-amino-2-methylpentane (Kp ^ g: 90-94 ° C), 2-cyclohexylamino-4-amino-2-methylpentane (Kp ^ g: 135-140 ° C), 2 -benzylamino-4-amino-2-methylpentane (Kp: 150-155 ° C), 2a-phenethyl-4-amino-2-methylpentane (KpQ

100..105 ° C) and 20-phenethylamino-4-amino-2-methylpentane (Kpg 101..105 ° C).

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The reaction of compounds of general formula II in which R represents a halogen atom with amines of general formula III or their acid addition salts is conveniently carried out in the presence of hydrogen halide acceptors, such as amines of formula III added to the reaction, tertiary amines, alkali metal bases or alkali carbons. Between 0 ° C and the boiling point of the reaction mixture, most preferably between 0 and 25 ° C.

The reaction mixtures are worked up either by suction filtration of sparingly soluble amides and / or by evaporation of the separated organic phase to a small volume.

The reaction of the compounds of the general formula II in which R represents an alkoxy group with the amines of the general formula III takes place at a higher temperature, e.g. at the boiling point of the reaction mixture in question.

After completion of the reaction, the crude amides are recovered by suction filtration or by evaporation of the clearly filtered reaction solutions to a small volume.

The reaction of compounds of general formula II in which R represents a halogen atom or an alkoxy group with amines of general formula III conveniently takes place in the presence of organic solvents, such as, for example, aromatic hydrocarbons, such as benzene or toluene, paraffinic hydrocarbons, e.g. n-hexane. in the presence of halogenated hydrocarbons such as carbon tetrachloride or trichlorethylene, lower aliphatic ketones such as acetone or methyl ethyl ketone, or alcohols such as ethanol or isopropanol or aqueous mixtures thereof.

Reaction of compounds of general formula II in which R represents a hydroxyl group with amines of general formula III with water-cleaving agents, e.g. dicyclohexylcarbodiimide, also gives amides of general formula I in inert organic solvents.

The crude products obtained by the methods described can be easily purified by recrystallization from suitable organic solvents such as, for example, ethanol, isopropanol, benzene, n-hexane, benzene or mixtures thereof.

The obtained compounds of the general formula can be modified by reacting them in a known manner with physiologically acceptable inorganic or organic acids used in equimolar or greater amounts, e.g. hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, formic acid, acetic acid, acetic acid , benzoic acid, succinic acid, salicylic acid, oxalic acid, malonic acid, adipic acid, maleic acid, fumaric acid, tartaric acid, citric acid or ascorbic acid to the corresponding acid addition salts.

If the amides of the general formula I are obtained in the form of difficult-to-crystallize oils or creams, the corresponding crystalline acid addition salts can be obtained by reacting these products with physiologically acceptable inorganic or organic acids in suitable organic solvents such as ethanol or isopropanol.

Hydrohalides of basic compounds of general formula I can be prepared directly by reacting equimolar amounts of compounds of general formula II in which R represents a halogen atom with amines of general formula III in suitable 565329 organic solvents such as e.g. benzene, halogenated hydrocarbons or hydrocarbons.

The compounds of general formula II used as starting materials can be prepared by the methods described in DD Patents 81,116 and 81,117.

Example 1 3- [41-Cyclohexylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7-dimethoxy-1-thia-isochromane-1,1-dioxide

To a suspension of 13.5 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide in 150 ml of toluene is added dropwise, with stirring and ice-cooling, a solution of 9.9 g of 2 -cyclohexylamino-4-amino-2-methylpentane in 25 ml of toluene and immediately thereafter under cooling with a solution of 2.0 g of sodium hydroxide in 50 ml of water. Stir for 2 hours at room temperature and extract the aqueous phase with toluene. After evaporation of the combined dried toluene solutions, the residual oil is crystallized and triturated with n-hexane to crystallize to colorless crystals with a melting point of 119-123 ° C.

Example 2 3 - [(4'-methylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thiaisochromane 1,1-dioxide

A mixture of 9.1 g of 3-carbomethoxy-6,7-dimethoxy-1-thia-isochromane-1,1-dioxide, 5.9 g of 2-methylamino-4-amino-2-methylpentane and 40 ml of benzene, heated for one hour with stirring at the boiling point and then suction filtered to a clear solution. Colorless crystals precipitate from the filtrate, which are filtered off with suction, washed with benzene and dried (6.2 g). After recrystallization from isopropanol, 3.5 g = 29.2% of the theoretical colorless 3 - [(4'-methylamino-41-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thia-isochroman-1,1 dioxide crystals melting at 157-162 ° C.

* Example 3 3- [4'-methylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thiaisochromane 1,1-dioxide

In analogy to the procedure described in Example 2, 10,66532 of 9.1 g of 3-carbomethoxy-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide and 5.9 g of 2-methylamino-4-amino are obtained. 2-methylpentane in the presence of trichlorethylene 3.8 g (31.7%) of the theoretical 3- [4'-methylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7-dimethoxy-1-thia- isochromane-1,1-dioxide with a melting point of 157-162 ° C.

Example 4 3- [4'-Methylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thiaisochromane 1,1-dioxide

To a suspension of 36.0 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide in 340 ml of toluene is added dropwise with stirring and ice-cooling to 2-10 ° C. , containing 18.2 g of 2-methylamino-4-amino-2-methylpentane in 60 ml of toluene and immediately followed by a solution of 5.8 g of sodium hydroxide in 150 ml of water.

It is then stirred for 2 hours at room temperature. The separated crystals are filtered off with suction, the toluene phase is separated off and evaporated to dryness. After crystallization of the combined crude products from isopropanol, Λ 7 2 6% to 38.9 g = 'theoretical 3- [4'-methylamino-4'-methylpentyl- (2') - carbamoyl] -6,7-dimethoxy-1-thia-isochroman -1,1-dioxide with a melting point of 145-151 ° C.

Analysis for C 18 H 28 N 2 O 6 S (MP: 400.5)

C H N S

calculated%: 53.98 7.06 6.99 8.01 found%: 53.98 7.18 6.79 8.05

Example 5 3- [4'-Methylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thiaisochromane 1,1-dioxide

In the same manner as in Example 4, 13.6 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochromane-1,1-dioxide and 7 g of 2-methylamino-4-amino-2- methylpentane in the presence of isopropanol 13.7 g (68.5% of theory) of 3- [4'-methylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thia-isochroman-1,1- dioxide. * S.p. 141-144 ° C.

ιι 56532

Example 6 3- [4'-Methylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thia-isochroman-1,1-dioxide

Using the same procedure as in Example H, 6.8 g of 3-chlorocarbonyl-6,7-dimethoxy-thia-isochroman-1,1-dioxide and 3.5 g of 2-methylamino-4-amino-2-methylpentane are obtained. in the presence of benzene at 18-25 ° C 6.3 g (63.1% of theory) of 3- [4'-methylamino-4 * -methylpentyl- (21) -carbamoyl] -7,7-dimethoxy-1-thia -isokromaani-1,1-dioxide. Mp 143-147 ° C.

Example 7 3- [4'-Methylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thiaisochromane 1,1-dioxide

By the same procedure as in Example 4, 13.6 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochromane-1,1-dioxide, 7.0 g of 2-methylamino-4-amino- 2-methylpentane and 21 g of potassium carbonate in the presence of carbon tetrachloride and water 4.4 g (22.0% of theory) of 3- [4'-methylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7-dimethoxy- 1-thia-isochroman-1,1-dioxide. Mp 142-145 ° C.

Example 8 3- (4'-Methylamino-4'-methylpentyl-2 ') - carbamoyl-7-6,7-dimethoxy-1-thiaisochromane 1,1-dioxide

By the same procedure as in Example 4, 6.8 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide are obtained in acetone and 3.5 g of 2-methylamino-4-amino. In the presence of 2-methyl-pentane 5.7 g (57.1% of theory) of 3- (4'-methylamino-4'-methylpentyl-2 ') - carbamoyl-7-6,7-dimethoxy-1-thia-isochroman-1 , 1-dioxide. Mp

149 DEG-154 DEG C.

Example 9 3- [4'-Methylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thia-isochroman-1,1-dioxide

By heating 6.8 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochromane-1,1-dioxide and 7.0 g of 2-methylamino-4-amino-2-methylpentane in 100 ml of anhydrous benzene and separating then precipitated 2-methylamino-4-2-methylpentane monohydrochloride is obtained in the same manner as in Example 4 after crystallization from isopropanol 12 S6532 5.65 g (56.6% of theory) of 3- [41-methylamino-4'-methylpentyl- (2 ') ) -karbamoyyli_7-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide. Mp

147..151 ° C.

Example 10 3-Methyl-3- [4'-methylamino-4'-methylpentyl- (2 ') - carbamoyl] -6,7-dimethoxy-1-thia-isochroman-1,1-dioxide dinitrate

To a solution of 4.15 g of crude 3-methyl-3- [4'-methylamino-4-methylpentyl- (2 ') - carbamoyl] -7,7-dimethoxy-1-thia-isochroman-1,1-dioxide, m.p. 78-80 ° C (prepared according to Example 3 from 3-methyl-3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide and 2-methylamino-4-amino-2-methylpentane) In 30 ml of isopropanol, 1 ml of concentrated nitric acid is added dropwise at 50 ° C. After cooling, 1.9 g (39.8% of theory) of 3-methyl-3- [4'-methylamino-4'-methylpentyl- (2S) -carbamoyl] -7,7,7-dimethoxy-1-thiazoisochroman-1, 1-dioxide nitrate with a melting point of 167..171 ° C.

Analysis for ^ 19H31NgOgS (MP: 477.5)

C H N S

calculated%: 47.79 6.54 8.80 6.71 found%: 47.88 6.67 8.64 6.78

Example 11 3- [41-n-Propylamino-4'-methyl-pentyl- (2 ') - carbamoyl] -7,7-dimethoxy-1-thia-isochroman-1,1-dioxide

In the same manner as in Example 1, 15.3 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide and 9.4 g of 2-n-propylamino-4-amino-2 -methylpentane in the presence of toluene 14.4 g of 4'-n-propylamino-4'-methyl-pentyl- (21) -carbamoyl-7-6,7-dimethoxy-1-thia-isochromane-1,1-dioxide.

C20H32N2 ° 6S MP: 1 + 28> 5 »δ · Ρ · ° C.

Example 12 3- [4'-n-Butylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7-dimethoxy-1-thia-isochromane 1,1-dioxide

In the same manner as in Example 1, 6.7 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochromane-1,1-dioxide and 4.5 g of 13 S6532 2-n-butylamino-4-amino are obtained. -2-methylpentane in the presence of toluene 8.2 g of 3- [4'-n-butylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thia-isochromane-1,1-dioxide.

C21H34N2O6S MP: 442'6 S.p. 117-121 ° C

Example 13 3- [4'-n-Hexylamino-4'-methylpentyl- (2 ') -carbamoyl] -7,7,7-dimethoxy-1-thia-isochroman-1,1-dioxide

In the same manner as in Example 1, 13.5 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thiaisochromane-1,1-dioxide and 10.0 g of 2-n-hexylamino-4-amino are obtained. 2-methylpentane in the presence of toluene 19.3 g of 3- [4'-n-hexylamino-4'-methylpentyl- (2S) -carbamoyl] -7,7,7-dimethoxy-1-thia-isochromane-1,1-dioxide.

C23H38N2O6S MP: 470> 6 S.p. 88-94 ° C

Example 14 3- [4S-Isobutylamino-4R-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thia-isochromane-1,1-dioxide

In the same manner as in Example 1, 13.5 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thiaisochromane-1,1-dioxide and 8.6 g of 2-isobutylamino-4-amino-2 -methylpentane in the presence of toluene 16.1 g of 3- [4'-isobutylamino-4 * -methylpentyl- (2 *) -carbamoyl] -7,7,7-dimethoxy-1-thia-isochromane-1,1-dioxide.

C21H34N2O6S MP: 442'6 S.p. 80-83 ° C

Example 15 3-7 4'-Isopropylamino-4'-methylpentyl- (2 ') - carbamoyl_7-6,7-dimethoxy-1-thiaisochromane 1,1-dioxide

In the same manner as in Example 1, 13.5 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thiaisochromane-1,1-dioxide and 7.9 g of 2-isopropylamino-4-amino-2-methylpentane are obtained in the presence of toluene 16.3 g of 3- [4'-isopropylamino-4'-methylpentyl- (2 *) -carbamoyl] -7,7-dimethoxy-1-thia-isochromane-1,1-dioxide.

C20H32N2 ° 6S MP: 428'5 S.p. 72-80 ° C

56532 14

Example 16 3- [4'-Sec-Butylamino-4'-methylpentyl- (2f) -carbamoyl] -7,7-dimethoxy-1-thia-isochromane-1,1-dioxide

In the same manner as in Example 1, 9.5 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochromane-1,1-dioxide and 6.2 g of 2-sec-butylamino-4-amino-2 -methylpentane in the presence of toluene 11.2 g of 3- [4'-sec-butylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7-dimethoxy-1-thia-isochromane-1,1-dioxide.

C21H34N2O6S MP: 442'6 S.p. 95-100 ° C

Example 17 3- [4'-β-Phenylethylamino-4'-methylpentyl- (2 ') - carbamoyl] -6,7-dimethoxy-1-thiaisochromane 1,1-dioxide

In the same manner as in Example 1, 11.6 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochromane-1,1-dioxide and 7.0 g of 2- 6-phenylethylamino-4-amino-2 -methylpentane in the presence of toluene by crystallization from n-hexane / benzene 3- [4,4-β-phenylethylamino-U'-methylpentyl- (2 ') - carbamoyl] -6,7-dimethoxy-1-thia-isochroman-1,1- dioxide.

C25H34N2O6S MP: 490'6 S.p. 115-118 ° C

Example 18 3- [4,1-Benzylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thiaisochromane-1,1-dioxide

In the same manner as in Example 1, 13.5 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thiaisochromane-1,1-dioxide and 10.3 g of 2-benzylamino-4-amino-2-methylpentane are obtained in the presence of toluene from n-hexane / benzene 3- [4'-benzylamino-4'-methylpentyl- (2 ') - carbamoyl] -6,7-dimethoxy-1-thia-isochromane-1,1-dioxide.

C24H32N2O6S MP: 476'6 S-P. 107-110 ° C

Example 19 3- (3'-Cyclohexylaminopropylcarbamoyl) -6,7-dimethoxy-1,1-thiaisochromane 1,1-dioxide

In the same manner as in Example 4, 13.5 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochromane-1,1-dioxide and 7.8 g of 56532 1-amino-3-cyclohexylaminopropane are obtained in the presence of toluene. 7.4 g of 3- (3'-cyclohexylaminopropylcarbamoyl) -6,7-dimethoxy-1-thiaisochromane 1,1-dioxide.

C20H30N2O6S MP: 426'5 M.p.80-88 ° C

Example 20 3- (3'-n-Propylaminopropylcarbamoyl) -6,7-dimethoxy-1-thiaisochromane 1,1-dioxide

In the same manner as in Example 1, 15.3 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thiaisochromane-1,1-dioxide and 7.8 g of 1-amino-3-n-propylaminopropane in the presence of toluene are obtained. 12.1 g of 3- (3'-n-propylaminopropylcarbamoyl) -6,7-dimethoxy-1-thia-iso-chromane-1,1-dioxide.

C17H26N2O6S MP: 386'5 S-P. 107-109 ° C

Example 21 3-Methyl-3- [4'-methylamino-4'-methyl-pentyl- (2 *) -carbamoyl] -7,7-dimethoxy-1-thia-isochromane-1,1-dioxide

In the same manner as in Example 1, 15.3 g of 3-methyl-3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide and 6.5 g of 2-methylamino-4-amino-2-methylpentane are obtained in the presence of toluene 4.6 g of 3-methyl-3- [4'-methylamino-4 * -methyl-pentyl- (2 ') - carbamoyl] -6,7-dimethoxy-1-thia-isochromane-1,1-dioxide.

C19H30N2O6S MP: S.p. 78-80 ° C

Example 22 3- [4'-n-Butylamino-4, -methylpentyl- (2 ') - carbamoyl] -7,7-dimethoxy-1-thia-isochroman-1,1-dioxide

In the same manner as in Example 1, 15.3 g of 3-methyl-3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide and 8.9 g of 2-n-butylamino-4 -amino-2-methylpentane in the presence of toluene 5.6 g of 3-methyl-3- [4, -n-butylamino-4, -methyl-pentyl- (2 ') - carbamoyl] -7,7-dimethoxy-1-thia- isochroman-1,1-dioxide.

C22H34N2O6S S.p. 102 ··· 111 ° C 56532 16

Example 23 3-Methyl-3- [4 * -isobutylamino-4'-methyl-pentyl- (2 ') - carbamoyl] -6,7-dimethoxy-1-thia-isochromane-1,1-dioxide

In the same manner as in Example 1, 30.6 g of 3-methyl-3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide and 20.6 g of 2-isobutylamino-4-amino-2-methylpentane are obtained in the presence of toluene 28.1 g of 3-methyl-3- [4'-isobutylamino-4'-methyl-pentyl-

(21) -karbamoyyli_7 ~ 6,7-dimethoxy-1-thia-isochroman-1,1-dioxide. C22H34N2O6S MP: 454> 6 S.p. 101-105 ° C

Example 24 3-Methyl-3- (31-cyclohexylamino-dihydro-carbamoyl) -6,7-dimethoxy-1-thia-isochroman-1,1-dioxide

In the same manner as in Example 1, 30.6 g of 3-methyl-3-chlorocarbonyl-6,7-dimethoxy-1-thiaisochromane-1,1-dioxide and 15.6 g of 1-amino-3-cyclohexylaminopropane in the presence of toluene are obtained using 18.6 g 3-methyl-3- (3'-cyclohexylaminopropylcarbamoyl) -6,7-dimethoxy-1-thiaisochromane 1,1-dioxide.

C21H32N2 ° 6S MP: 4U0'6 S.p. 74-78 ° C

Example 25 3-Methyl-3- (3'-n-propylaminopropylcarbamoyl) -6,7-dimethoxy-1-thiaisochromane 1,1-dioxide

In the same manner as in Example 1, 30.6 g of 3-methyl-3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochromane-1,1-dioxide and 11.6 g of 1-amino-2-n-propylaminopropane in the presence of toluene are obtained 13.2 g of 3-methyl-3- (3N-propylaminopropylcarbamoyl) -6,7-dimethoxy-1-thiaisochromane-1,1-dioxide.

C 18 H 28 N 2 O 6 S MP: 1 + 00 »5 S.p. 112-117 ° C

Preparation of salt

Example 26 3- (4'-Methylamino-4 '' - methylpentyl- (2 ') - carbamoyl) -7,7,7-dimethoxy-1-thia-isochromane 1,1-dioxide-nitrate

In the same manner as in Example 10, 4.0 g of 3, - ^ ~ 4'-56532 17 are obtained

methylamino-4'-methyl-pentyl- (2 ') - carbamoyl-7-7,7-dimethoxy-1-thia-isochroman-1,1-dioxide in isopropanol solution and adding 1 ml of concentrated nitric acid 4.18 g 3- / 4 '-methylamino-4-methylpentyl- (2') - carbamoyl_7-6,7-dimethoxy-1-thia-isochromane 1,1-dioxide nitrate. C18H29N3O9S MP: 463'5 S.p. 177-180 ° C

Example 27 3- [4 1-Methylamino-4-methylpentyl- (2 1) -carbamoyl] -7,7,7-dimethoxy-1-thia-isochromane 1,1-dioxide-hydrogen sulfate

In the same manner as in Example 10, 2.0 g of 3- [4'-methylamino-4-methylpentyl- (2S) -carbamoyl] -7,7-dimethoxy-1-thia-isochromane-1,1-dioxide in isopropanol are obtained and by dropwise addition of 1 ml of concentrated sulfuric acid 0.77 g of 3- [4'-methylamino-4-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thia-isochromane-1,1-dioxide-hydrogen sulphate .

C 18 H 29 N 2 O 10 S 2 MP: 498.6 S, p * 174 ··· 185 ° C

Example 28 3- [4'-Methylamino-4-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thiaisochromane 1,1-dioxide fumarate

In the same manner as in Example 10, 2.0 g of 3- [4 * -methylamino-4-methylpentyl- (2f) -carbamoyl-7-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide in ethanol solution are obtained and added 0.58 g of fumaric acid 1.35 g of 3-74'-methylamino-4-methylpentyl- (2 *) -carbamoyl-7-6,7-dimethoxy-1-thia-isochromane-1,1-dioxide-fumarate.

C22H31N2 ° 10S MP: 515.6 S, p · 217 ··· 220 ° c-

Example 29 3- [4 * -α-Phenylethylamino-4'-methylpentyl- (2 *) -carbamoyl] -7,7,7-dimethoxy-1-thia-isochromane-1,1-dioxide-fumarate

In the same manner as in Example 10, 2.5 g of crude 3- [4-α-phenylethylamino-4'-methyl-pentyl- (2 ') - carbamoyl] -7,7-dimethoxy-1-thia-isochromane-1,1-dioxide are obtained using in ethanol and adding

0.5 g of fumaric acid 0.9 g of 3- [4 * -α-phenylethylamino-4'-methylpentyl- (2 ') - carbamoyl] -7,7,7-dimethoxy-1-thia-isochromane-1,1-dioxide-Fuma -raattia. QS MP: 606.7 S.p. 120-122 ° C

Claims (2)

56532 18 A process for the production of psychotropically active 3-carbamoyl-1-thia-isochromane-1,1-dioxide derivatives of the general formula Vg - ^ r1 (I) I ^ C ^ R3 CH0 * c3 Ας yO ^ NH-CH-CHO -C-NH-R0% o'l L »li 0 ^ ^ 0 RR wherein 1 4 R ... R 1 are the same or different from each other and denote a hydrogen atom or a methyl group R 1 denotes a straight-chain or branched alkyl group having 1. To prepare a C 6 atom, a benzyl, β-phenylethyl or cyclohexyl group and their acid addition salts with physiologically acceptable inorganic and organic acids, characterized in that the general formula R 1 is CH 3 ° / 0 ^ ai) CH 3 ° / 0 ^ wherein R is the same as defined above and R is a halogen atom such as chlorine or bromine, or a hydroxy or alkoxy group, the compounds of the general formula R 3 are reacted with R 3 H «N - CH - CHO - C - NH - R 5 (III) R 2 R4 56532 19 oqhc,. ... wherein R, R, R and R are as defined above, with the amines or their acid addition salts and if the compounds of the general formula I obtained, if obtained in the form of bases, are, if desired, converted into their acid addition salts with physiologically acceptable inorganic or organic acids. For example, 3-carbamoyl-1-thia-isochroman-1,1-dioxide is derivatized with the formula βΗ R1 CHqO 2vC2. (I) I ^ C ^ R3 CH-O L " 2 O * ^ 0 där 1 HR ... R ärmbördes lika eller olika ooh betecknar en väteatom eller en methyllupp 5 R betecknar en rak kedja eller förgrenad alkylgrupp med 1 ... 6 kolatomer, en benzyl-, β-penyletyl- eller the cyclohexyl group, as the case may be treated with physiologically active organic and organic syrups, is preferably treated with the compounds of the formula CH o - r1 ^ ° uh3u - c ^ (II) I \ r6 CH3 ° ~ S ^ \ s ^ 0 o 1. from R is a mixture of ova and R with a halogen atom consisting of chlorine or bromine, or hydroxy- or alkoxy group, which react with