DE1133381B - Process for the preparation of phentiazine derivatives substituted in the 3-position by sulfur-containing groups - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY KL. 12 ρ 4

INTERNAT. KL. C 07 d

GERMAN

PATENT OFFICE

EXPENDITURE 1133 381

S57847IVd / 12p

REGISTRATION DATE: 15 A P R I L 1958

NOTICE
THE REGISTRATION
CND OUTPUT
EDITORIAL: JULY 19, 1962

The subject of patent application S 52 942 IVd / 12p (German Auslegeschrift 1 128 856) is a method for the production of in 3-position by sulfur-containing Groups-substituted phenthiazine derivatives of the general formula

Method of manufacture

from in 3-position through sulphurous

Groups substituted phentiazine derivatives

Addition to patent application S 52942 IVd / 12 ρ (Auslegeschrift 1128 856)

CH ₂

CH ₂

CH-R ₄ ,

I )

NH-R ₃ "

wherein R _{1 is} a hydrogen atom or an alkyl group, a phenyl group or an aralkyl group, R _{2 is} a hydrogen atom or an alkyl group, R _{3 is} a hydrogen atom or an alkyl group and R _{4 is} a hydrogen atom or R ₃ and R _{4 are} - (CHu) ₃ - or - (CHa) ₄ -GrUpPe, where, if R _{1 is} a methyl group, R ₄ cannot be a hydrogen atom, which is characterized in that phenthiazines of the general formula Applicant:
Sandoz AG, Basel (Switzerland)

Representative: Dr. W. Schalk, Dipl.-Ing. P. Wirth,

Dipl.-Ing. G. E. M. Dannenberg

and Dr. V. Schmied-Kowarzik, patent attorneys, Frankfurt / M., Große Eschenheimer Str. 39

Claimed priority:

Switzerland of April 17, May 29 and December 18, 1957 (No. 45 144, No. 46 703 and No. 53 884)

Dr. Jany Renz, Dr. Jean-Pierre Bourquin, Dr. Erhard Schenker and Gustav Schwarb,

Basel (Switzerland), have been named as inventors

It has been found that such compounds of the general formula I,

SR ₁

wherein R _{1 has} the above meaning with a primary, secondary or tertiary co-haloalkylamine of the general formula

! -SR ₁

CH, - CHo - CH. - N - CH ₃

i;
XCH ₂ -CH ₂ -CH-NR ₂

where R _{1 is} an alkyl group with 1 to 3 carbon atoms, R ₂ and R ₃ together are - (CHg) ₃ - or where R ₂ , R ₃ and R _{4 have the} above meaning and X - (CH ₂ ) ₄ group or, if R ₁ denotes no methyl chlorine or bromine atom, condensed and 50 denotes the remainder, R ₂ denotes a hydrogen atom and R ₃ denotes an optionally benzyl mercapto group reductive methyl group, cleaves in a manner known per se to form the sulfhydryl group. also obtained by using derivatives of phenthiazine

209 620/308

10-carboxylic acid halides of the general formula II,

-SR ₁

that in the case of phenthiazine derivatives which have an ethyl mercapto group in the 3-position of the phenthiazine structure, the adrenolytic effect is most pronounced. Those made by the present process 5 substances can either per os in dragees or tablets or parenterally, z. B. subcutaneous, administered ; be enough.

CO Hai In the examples below showing the procedure

explain, the melting and boiling points are unworin Hai stands for a chlorine, bromine or iodine atom, 10 corrected, with an aminoalkanol of the general formula III, example 1

HO - CH ₂ - CH ₂ - CH-N - CH,

converts and the esters of the general formula IV thus obtained,

CO-O-CH ₉ -CH ₂ -CH-N-CH,

IV

carbon dioxide is split off by heating to a temperature of about 150 to 220 ^° _{C., where R 1} , R ₂ and R ₃ in formulas II, III and IV have the same meaning as in formula I.

The process is carried out, for example, by using an alkyl mercapto-phenthiazine-10-carboxylic acid halide of formula II in a suitable solvent such as benzene, toluene, xylene,

A solution of 93 g of phosgene in 450 ecm of toluene is added all at once at room temperature to a solution of 115 g of 3-methylmercaptophenthiazine with a melting point of 138 to 140 ° C. in 2250 ecm of benzene. The reaction mixture is heated to boiling in a water bath for one hour. After a further 3 hours of refluxing, the solvent is evaporated off under reduced pressure and the evaporation residue is rapidly recrystallized from 100ccm of boiling absolute ethanol, cooled and suction filtered. The analytically pure 3-methylmercapto-phenothiazine-lO-carboxylic acid chloride has the melting point 122 to 124 ⁰ C.

A mixture of 25.0 g of 3-methylmercapto-phenthiazine -10-carboxylic acid chloride, 23.2 g of 1-methyl-2 OS-hydroxyethyl) piperidine (boiling point ₇₆₀ 233 ° C.) and 200 ecm of benzene is heated at 120 for 15 hours ⁰ C bath temperature boiled under reflux. After cooling, the reaction mixture is extracted twice with 70 ecm of water each time and then with 80 ecm of 15% tartaric acid. The collected extracts are shaken out with 100 ecm of benzene and finally made phenolphthalic alkaline with 30 ecm of concentrated sodium hydroxide solution. The precipitated base is taken up in 300 ecm benzene, the benzene layer is washed with 100 ecm water, ge over potash

dries and evaporated under reduced pressure. Dichlorobenzene, nitrobenzene, dissolves and with a 40 The evaporation residue is dissolved in 180 ecm isopropanol amino alcohol of the formula III, optionally dissolved in one and dissolved with isopropanolic hydrochloric acid up to the above solvent, at room temperature treated with Congo acidic reaction. The precipitated temperature or elevated temperature is converted and the salt is filtered off with suction and isolated from the reaction product of the formula IV boiling at 1600 ecm. The alkyl isopropanol recrystallizes. The analytically pure Hymercapto ^ phenthiazia-10-carboxylic acid ester of the formula 45 hydrochloride of 3-methyhnercapto-phenthiazine-10-car-IV is then heated to temperatures of about 150 to bonsäure - {ß- [N'-methylpiperidyl- (2 ')] - ethyl} - ester 22O ⁰ C heats, melts cleaved whereby carbon dioxide at 197-199 ° C with decomposition and entwird. If appropriate, the reaction can be carried out in ¹ J ₂ mol of water of crystallization.

Suitable solvents such as dichlorobenzene or nitro- The base is prepared by adding 5.7 g of the

benzene. After the end of the 5 ° above hydrochloride dissolves in 100 ecm of water, with carboxylation makes the new phenthiazine derivatives 3n-ammonia phenolphthalein alkaline and of the formula I isolated or, if appropriate, taking up the precipitated base in its salts in 50 ecm benzene, convicted. After washing the benzene solution with 25 ecm of water

The so far produced by the new process is dried over potash, filtered and in the unknown basic phenthiazine derivatives are freed from the solvent at 55 vacuum. Evaporation of the room temperature oily or crystalline form and with inorganic residue is from 300 cc of boiling petroleum ether and organic acids crystalline (Kp. 40 to 6O ⁰ C) recrystallized. Analytically pure stable salts. Base, the S-methylmercapto-phenthiazm-10-carbon-

The compounds prepared according to the method acid- {J8 [N'-methylpiperidyl (2 ')] - ethyl} ester, possess pharmacodynamic properties varied melts 60 at 77 to 79 ⁰ C.

stocks. Their strong adrenolytic effect is 4.99 g S-methylmercapto-phenthiazine-10-carbon-

characteristic, which are the des 3-chloro-lO- acid - {/ 3- [N'-methylpiperidyl- (2 ')] - ethyl} esters {j5- [N'-methylpiperidyl- (2')] - ethyl} -phentbJazins exceeded in an oil bath for 1 hour at 180 ⁰ C, and then applies (the patent application S see. thereto IVd 52,942 / 4 hours at 200 ⁰ C under the vacuum of a water-12p [German Auslegeschrift 1,128,856]) . They are said to be heated to 65 jet pumps. After the end of the carbon, therefore, in therapy to combat the splitting off of earth dioxide, the piston residue is used in conditions of tension and tension in a psychological high vacuum under a pressure of 0.02 mm Mercury diseases. It has been shown, silver column distilled at 228 to 323 ⁰ C. The analytical

Pure base, 3-methylmercapto-10 - {/ S- [N'-methylpiperidyl- (2 ')] - ethyl} -phenthiazine, boils under a pressure of 0.02 mm of mercury at 230 ° C. From four times the amount Recrystallized from boiling isopropanol, the constant melting point of the base is 72 to 74 ° C. Yield: about 80% (always calculated from the acid chloride to the “decarboxylated” phenthiazine). 3 - methylmercapto -10 - {ß [N '- methylpiperidyl (2')] - ethyl} -phenthiazin hydrochloride: mp 158 to 16O ⁰ C, sinters from 153 ° C.

Example 2

A solution of 106 g of phosgene in 450 ecm of toluene is added all at once at room temperature to a solution of 146 g of 3-isopropylmercaptophenthiazine (melting point 118 to 120 ° C.) in 1000 ecm of benzene. The reaction mixture is heated to boiling in a water bath for one hour. After a further 3 hours of refluxing, the solvent is evaporated off under reduced pressure and the evaporation residue is taken up warm in petroleum ether (boiling point 40 to 60 ° C.) and filtered. After concentrating the filtrate in vacuo to about 11, this solution is left to stand in the ice box overnight. The crystals are suction filtered and quickly recrystallized from 150 ecm warm absolute ethanol and cooled. The analytically pure 3-isopropylmercapto-phenothiazine-10-carboxylic acid chloride melts with decomposition at 62 to 64 ⁰ C.

A mixture of 22.46 g of 3-Isopropylmercaptophenthiazin-10-carboxylic acid chloride, 19.1 g of l-methyl-2- (iS-hydroxyethyl> piperidine (Kp _{7. 60:} 233 ° C) and 175 cc of benzene for 15 hours at heated to 120 ° C bath temperature to boiling under reflux. After cooling, the reaction mixture twice ecm with 70 water, is then treated with 75 cc shaken 15 ° / _o tartaric acid. the collected extracts are extracted by shaking with 75 cc of benzene and finally with 30 cc concentrated caustic soda made phenolphthalein alkaline.

The precipitated base is taken up in 250 ecm benzene, the benzene layer is washed with 75 ecm water, dried over potash and evaporated under reduced pressure. The evaporation residue is dissolved in 150 ecm isopropanol and mixed with isopropanolic hydrochloric acid until the Congo acidic reaction occurs. The precipitated salt is suction filtered and recrystallized from 225 ecm boiling isopropanol. The analytically pure hydrochloride of 3 - isopropylmercapto - phenthiazine -10 - carboxylic acid {ß - [N '- methylpiperidyl - (2')] - ethyl} - ester melts with decomposition at 115 to 117 ⁰ C after sintering at 100 ⁰ C.

24.31 g of 3-isopropylmercapto-phenthiazine-10-carboxylic acid {/? - [N '- methylpiperidyl - (2')] - ethyl} - ester, prepared from pure hydrochloride, are in an oil bath at ISO ⁰ C for 1 hour and then heated for 4 hours at 200 ^° C. under the vacuum of the water jet pump. After the elimination of carbon dioxide has ended, the flask residue is distilled ^{at 222 to 225 ° C. under a pressure of 0.005 mm of mercury under a high vacuum.} The analytically pure base, the 3-isopropylmercapto-1 0- {ß ~ [N'-methylpiperidyl (2 ')] - ethyl} -phenthiazin boiling boiling under a pressure of 0.005 mm Hg at 223 ⁰ C. From three times the amount of Isopropanol recrystallized, the constant melting point of the base is 73 to 75 ^° C. Yield about 70%.

Example 3

A mixture of 32.1 g of 3-ethylmercapto-phenthiazine-10-carboxylic acid chloride (melting point 95 to 97 ° C.), 28.6 g of l-methyl-2 - (/ 3-hydroxylethyl) piperidine (b.p. ₇₀₀ 233 ⁰ C) and 200 cc of benzene is heated "for 15 hours at 120 ⁰ C bath temperature to boiling under reflux. After cooling, the reaction mixture with 70 cc of water and then twice with 150 cc of 15% tartaric acid is shaken. the collected extracts are still shaken out with 40 ecm benzene and finally made with 60 ecm concentrated sodium hydroxide solution phenolphthaleinalkaliseh. The precipitated base is taken up in 450 ecm benzene, the benzene layer washed with 60 ecm water, dried over sodium sulfate and evaporated in vacuo. The evaporation residue is dissolved in 70 ecm isopropanol and mixed with isopropanolic hydrochloric acid until the Congo acid reaction occurs, and the precipitated hydrochloride is filtered off

so and recrystallized from 20 ecm boiling isopropanol. The analytically pure hydrochloride of 3-ethylmercapto-phenthiazine-10-carboxylic acid-f / S-IN'-methylpiperidyl- (2 ')] - ethyl} ester melts with decomposition at 147 to 149 ° C and contains Va mol of water of crystallization.

The free base is obtained by adding 3N ammonia to the aqueous solution of the hydrochloride until a phenolphthalein-alkaline reaction is achieved, the precipitated base is taken up with benzene and the dried benzene solution is evaporated. 3-Ethyl mercapto -10 - {ß - [N '- methylpiperidyl - (2')] - ethyl} -phenthiazine is obtained by decarboxylation of the ester base according to the _{method described in p <Example 2.} Kp _{0, 00} 8 of the pure base 225 ⁰ C. Yield about 80% · Pas tartrate melts at 135 ⁰ C with decomposition, after sintering above 7O ⁰ C.

Example 4

A mixture of 12.9 g of 3-ethylmercapto-phenthiazine-10-carboxylic acid chloride (mp 95 to 97 ° C), 10.4 g of l-methyl-2- (is-hydroxyethyl) pyrrolidine (bp ₁₁₁ 95 to 96 ° C) and 100 ecm of benzene is heated to boiling under reflux at a bath temperature of ^{12O 0 C for 15 hours.} After cooling, the reaction mixture is extracted with 70 ecm of water and then twice with 75 ecm of 15% aqueous tartaric acid each time. The collected extracts are shaken out with 60 ecm of benzene and finally made alkaline with 45 ecm of 28% aqueous ammonia. The precipitated base is taken up all at once in 750 ecm of benzene, the benzene layer is washed with 40 ecm of water, dried over sodium sulfate and evaporated in vacuo. The evaporation residue is dissolved in 20 ecm isopropanol and mixed with isopropanolic hydrochloric acid until the Congo acidic reaction occurs. The precipitated hydrochloride is filtered off and recrystallized from 100 ecm boiling isopropanol. The analytically pure hydrochloride of S-ethylmercapto-phenthiazine-10-carboxylic acid - {ß - [N '- methylpyrrolidyl - (2')] - ethyl} ester melts at 75 to 77 ° C with decomposition and contains 1 mol of water of crystallization. The salt melts after drying in a high vacuum at 146 to 148 ° C.

The free base is obtained by adding 3N ammonia to the aqueous solution of the hydrochloride up to the phenolphthalein alkaline reaction, taking up the precipitated base with benzene and Evaporation of the dried benzene solution. By decarboxylation of the ester base according to the method in Example 2

7 8

described method is obtained 3-Ethylmer- vapor residue is boiled with the calculated amount of capto - 10 - {ß - [N '- methylpyrrolidyl - (2')] - ethyl} - fumaric acid in absolute ethanol, wophenthiazine. Kp _{0, 01} of the pure base 213 ° C. Yield after the salt crystallizes on cooling. The ausetwa 80% · The tartrate melts at 90 ° C under fallen salt is filtered off and recrystallized 5 rapidly ethanol from absolute decomposition, after sintering above 7O ⁰ C.. The analytically pure

S-ethyl mercapto-phenthiazine-lO-carbon- fumarate

Example 5 Acid (γ-dimethylaminopropyl) ester melts at 133

A mixture of 21.5 g of 3-methylmercapto-phen- up to 135 ° C and contains 1 mol of water. thiazine-10-carboxylic acid chloride (M.p. 122 to 124 ° C), 4.45 g of 3 - ethyl mercapto - phenthiazine -10 - carbon-

18.0 g of 1-methyl-2 - ((S-hydroxyethyl) pyrrolidine (bp. _U i ° acid (y-dimethylaminopropyl) ester are below 95 to 96 ⁰ C) and 300 ecm of benzene is under a pressure of 15 mm of mercury in 15 hours at 120 ⁰ C bath temperature to reflux oil bath for 1 hour at 18O ⁰ C and then for 4 hours heated to boiling. After cooling, which is heated to 200 ° C. After completion of the coal reaction mixture with 150 cc of water and The residue is then split off with 100 ecm 15% aqueous tartaric acid and shaken under a pressure of 0.008 mm mercury. The collected extracts are still distilled in a silver column at 199 to 201 ° C. The analyzes are extracted with 100 ecm benzene and finally with pure Base, the 3-ethylmercapto-10- (y-dimethylamino-35 ecm concentrated sodium hydroxide solution phenolphthalein-propyl) -phenthiazine, boils under a pressure of alkaline. The precipitated base is made on 0.008 mm mercury column at 200 ^° C. Yield once in 250 e cm benzene was added, the benzene 20 about 75%. 3-Ethylmercapto-10- (y-dimethylamino layer washed with 150 ecm of water, over sodium propyl) -phenthiazine tartrate F. 117 to 119 ° C (dried sulfate and evaporated in vacuo. ^ The settlement), after sintering above 110 ° C. Evaporation residue is crystallized from 80 ecm 95% ethanol. After recrystallization from Example 7, 50 ecm 95% ethanol, the analytical 25 is obtained

pure base, the S-methylmercaptophenthiazine-10-car- A mixture of 15.0 g of 3-isopropylmercapto-

bonsäure - {ß - [N '- methylpyrrolidyl - (2')] - ethyl} - phenthiazine-10-carboxylic acid chloride (mp 62 to 64 ⁰ C), ester ( ^{mp 101 to 103 0} C). 9.2 g γ-dimethylaminopropanol and 150 ecm benzene

17.8 g of pure base are dissolved in 100 cc of absolute is dissolved during 15 hours at 120 ⁰ C bath temperature of ethanol and heated with ethanolic hydrochloric acid to 3 ° to boiling under reflux. Added to the Congo acidic reaction after the abortion. The precipitated cool, the reaction mixture with 120 ecm of hydrochloride is suction filtered and recrystallized from 150 ecm of water and then with 75 ecm of 15% aqueous boiling absolute ethanol. The tartaric acid shaken out. The collected extracts of analytically pure 3-methyl mercapto hydrochloride are shaken out with 80 ecm benzene and finally phenthiazine - 10 - carboxylic acid - {ß - N '- methylpyrro- 35 with 25 ecm concentrated sodium hydroxide solution phenolphthalidyl (2')] - ethyl} ester melts at 205 to 207 ⁰ C made pure alkaline. The precipitated base is decomposed. absorbed at once in 250 ecm benzene, the

Car- washed benzene layer with 120 cc of water, over bonsäure - - 20.0 g of 3 - methylmercapto - phenthiazine - 10 {ß - [N '- methylpyrrolidyl - (2')] - ethyl} - sodium sulfate dried and concentrated in vacuo to eingeester a pressure of 15 mm of mercury 40. Evaporation of the residue is dissolved in 60 cc column silver in an oil bath for 1 hour at 18O ⁰ C and absolute ethanol and heated with ethanolic followed by 4 hours at 200 ⁰ C. Added to hydrochloric acid until the Congo acid reaction occurs. The precipitated hydrochloride is filtered off and the residue is recrystallized in a high vacuum under a pressure of from boiling absolute ethanol. 0.008 mm mercury column at 208 to 210 ° C distilled 45 The analytically pure hydrochloride of 3-isopropylated. The analytically pure base, the 3-methylmercapto mercapto-phenthiazine-10-carboxylic acid - (γ-ai- 10 - {ß - [N '- methylpyrrolidyl - (2')] - ethyl} - phenmethylaminopropyl) ester melts under Decomposition thiazine, boils under a pressure of 0.008 mm at 180 to 182 ° C.

Mercury column at 209 ⁰ C. Yield about 70% 15.0 g of 3 - isopropyl mercapto - phenthiazine - 10-car-

3 - methyl mercapto - 10 - {ß - [N '- methylpyrrobonic acid (γ-dimethylaminopropyl) esters are found under lidyl - (2')] - ethyl} - phenthiazine tartrate: mp 115 ° C. a pressure of 15 mm of mercury in a decomposition, after sintering above 70 ⁰ C. oil bath for 1 hour at 180 ⁰ C and then for 4 hours

_. . _t heated to 200 ^{° C.} After finishing the coal

Example, the elimination of dioxyde is the residue in the high-

32, LG3 Äthylmercapto-phenothiazine-10-carboxylic acid 55 vacuum under a pressure of 0.01 mm mercury chloride (F. 95 to 97 ° C), 20.6 g of y-dimethylamino silver column at 197-199 ⁰ C distilled. _{The analytical propanol} (bp 76O 163 to 164 ° C) and 300 ecm benzene pure base, the 3-isopropylmercapto-10- (y-dimethyl become ^{aminopropyl) -phenthiazine for 15 hours at a bath temperature of 120 0} C, boils under a pressure under reflux Boiling heated. After the cool exhaust of 0.01 mm of mercury at 198 ⁰ C. Yield is the reaction mixture once with 100 cc of 60% about 70 ·

Water, then twice with 100 ecm 15% aqueous When adding a solution of 15.0 g base in

shaken out tartaric acid. The extracts are shaken out 150 ecm absolute ethanol with a solution of with a total of 40 ecm benzene and 5.3 g oxalic acid in 150 ecm absolute ethanol is then obtained with 40 ecm 28% ammonia alkaline to give the oxalate. Made out after recrystallization. The precipitated base is all at once 65,900 ecm of methanol, the analytically pure is taken up in 900 ecm of benzene, the benzene solution oxalate of 3-isopropylmercapto-10- (γ-dimethylamino is washed with 60 ecm of water, over sodium sulfate propyl) -phenthiazine (decomposition product 206 until dried and evaporated in vacuo. The one 208 ⁰ C). 3 - isopropyl mercapto - 10 - (γ - dimethyl-

aminopropyl) - phenthiazine - tartrate - hemihydrate: F. 9O ⁰ C (decomposition), after sintering above 6O ⁰ C.

Example 8

A mixture of 15.0 g of S-isopropylmercapto-phenthiazine-10-carboxylic acid chloride, 11.5 g of 1-methyl-2- (β-hydroxyethyl) pyrrolidine and 250 ecm of benzene is refluxed for 15 hours at a bath temperature of 120 ° C heated to boiling. After cooling the reaction mixture with 120 cc ίο water and then with 75 cc of 15 ° / ₀ aqueous tartaric acid is shaken. The collected extracts are shaken out with 80 ecm of benzene and finally made phenolphthalein alkaline with 25 ecm of concentrated sodium hydroxide solution. The precipitated base is taken up all at once in 250 ecm benzene, the benzene layer is washed with 120 ecm water, dried over sodium sulfate and evaporated in vacuo. The evaporation residue is dissolved in 60 ecm of absolute ethanol, mixed with ethanolic hydrochloric acid until the Congo acid reaction occurs and then with 60 ecm of ether. The crystallized hydrochloride is dissolved in 35 ecm warm ethanol, filtered and the warm filtrate is treated with 70 ecm ether. The analytically pure hydrochloride of 3-Isopropylmercaptophenthiazin -10 - carboxylic acid - {β - [N '- methylpyrrolidyl- (2')] - ethyl} ester melting at 179 to 181 ⁰ C with decomposition.

20.0 g of 3 - isopropylmercapto - phenothiazine-10-carboxylic acid - {ß - [N '- methylpyrrolidyl - (2')] - ethyl} ester are under a pressure of 15 mm Hg in an oil bath for 1 hour at 18O ⁰ C and then heated ^{to 200 °} C. for 4 hours. After the elimination of carbon dioxide has ended, the residue is distilled at 216 ° to 218 ° C. in a high vacuum under a pressure of 0.008 mm of mercury. The analytically pure base, 3-isopropyl mercapto - 10 - {ß - [N '- methylpyrrolidyl - (2')] - ethyl} -phenthiazine, boils under a pressure of 0.008 mm of mercury at 217 ° C. Yield about 70% · 3 - Isopropyl mercapto - 10 - {ß - [N '- methylpyrrolidyl - 2')] - ethyl} - phenthiazine - tartrate - hemihydrate: F. 9O ⁰ C (decomposition), after sintering above 7O ⁰ C.

Claims (1)

PATENT CLAIM: Modification of the process for the production of 3-position by sulfur-containing groups substituted phenthiazine derivatives of the general formula I, 45 CH ₂ - CH ₂ - CH-N - CH.,
R ₂ 50 55 wherein R _{1 is} an alkyl group with 1 to 3 carbon atoms, R ₂ and R ₃ together are a - (CH ^ ₃ - or - (CH ₂ ) ₄ group or, if R _{1 is} not a methyl radical, R _{2 is} a hydrogen atom and R ₃ denotes a methyl group, according to patent application S 52942 IVd / 12p (German Auslegeschrift 1 128 856), characterized in that derivatives of phenthiazine-10-carboxylic acid halides of the general formula II, - / N χ
CO - Hal -SR ₁ wherein Hal stands for a chlorine, bromine or iodine atom, with an aminoalkanol of the general Formula III, HO - CHo - CH ₂ - CH-N - CH, III converts and the esters of the general formula IV thus obtained, -SR ₁ CO-O-CH ₂ -CH ₂ -CH-N-CH ₃ IV carbon dioxide is split off by heating to a temperature of about 150 to 220 ° C., where R ₁ , R ₂ and R ₃ in formulas II, III and IV have the same meaning as in formula I. Considered publications:
German patent specification No. 939 630. Legacy Patents Considered:
German Patent No. 1,058,998. 20Ϊ 620/308 7.62