DE1620528A1 - Process for the preparation of new basic substituted s-triazines - Google Patents

Description

1O / me / e.g.
Case 5/312

Dr. Karl Inomae GmbH, Biberach an der Riss

Process for the production of new basic substituted

s-triazines

The invention relates to a process for the preparation of new basic substituted s-triazines of the formula

R -

In this formula, the radical R denotes a lower alkyl group, which is still due to a basic radical of the formula

—S

may be substituted, an alkenyl, alkylthioalkyl or alkoxyalkyl, aralkyl, aryl, alkoxy, lower acyl or an aroyl group. The radicals R ^ and R ₂ , which are the same or different

008-824 / 1946

BATH ORIGINAL

can be different, "mean alkyl! mercapto groups with οίε to 6 carbon atoms or saturated or unsaturated, branched or unbranched alkoxy groups with up to 6 carbon atoms, which can be substituted by a basic radical of the formula II, or basic radicals of the formula II, in which the radicals R, and R, which can be the same or different, unbranched or branched alkyl radicals with up to 10 carbon atoms, which can optionally be substituted by lower alkoxy, alkylthio or Kono or dialky amino groups, alkenyl radicals, Aralkyl radicals, aryl radicals, which can optionally be substituted on the aromatic ring by hydroxyl, alkoxy, lower alkyl groups or halogen atoms, or mean cycloalkyl radicals, where the radical R ^ can also be a 7 / hydrogen atom; R- and R. can also be together with the nitrogen atom form a heterocyclic A- to 7-membered ring which is interrupted by an oxygen atom and replaced by lower alkyl, hydr oxy or aralkyl groups can be substituted.

The new compounds are obtained by optionally stepwise reaction of s-triazines of the general formula

III,

in which the radicals A ₁ , A ₂ , A are halogen atoms and / or alkyl mercapto and / or alkoxy G groups, with one mole or a slight excess of a piperazine of the formula

IV,

F- J

009824/1945

BAD ORiGiNAL

in which the radical R has the meanings mentioned at the beginning, and optionally with 1-2 KoI or a slight excess one or two amines of the formula

' ^S 3

in which the radicals R- and R, which have meanings mentioned at the beginning, and / or if A ^ and / or A _{2 are} a calogen atom, with compounds of the formula R "H and R ₂ H, where R ^ and R ₂ , which may be the same or different, have the meanings mentioned at the beginning except that of a basic radical of the formula II. '

The exchange of an alkyl mercapto or an alkoxy group against an amino group is generally slower, but also more selective than the exchange of a chlorine atom against an amino group.

The reactions are advantageously carried out in aqueous suspension or in an organic solvent, for example acetone, methanol, ethanol, dioxane, benzene or tetrahydrofuran and, if there are halogen atoms, expediently in the presence of an acid-binding agent. The reaction temperature depends on the reactivity of the compounds of the general formula RH or R ^ H and also on whether the first, second or third halogen atom or the first, second or third alkylmercapto or alkoxy group is split off; In general, it is between - '.G ⁰ and -r ISC ⁰ O. The exchange of a halogenated for one of the specified 3 groups in the presence of a hydrogen halide binding agent generally takes place between -10 ° and + 120 "O, the exchange of a keroapto group or an alkoxy group for a radical of the formula II at temperatures between 50 ° and IcO ⁰ G. When using a compound he formula RH and / or R ₉ H with a lower boiling point

BATH ORIGINAL

the reaction is expediently carried out in a closed vessel

As a snure-binding agent can be an inorganic or tertiary organic base can be used. Palls R-. and / or Rp a A radical of the formula II can also be an at least molar excess of the compound of the formula V as an acid-binding agent to serve. A further excess of this amine can also be used as a solvent be used. When converting alcohols or mercaptans, the corresponding alkali or alkaline earth alcoholate is used or mercaptide as an acid binding agent. Alcohols and mercaptans can also be used in the presence of alkali or Alkaline earth hydroxides, carbonates or bicarbonates, which optionally can also be added to the reaction mixture in solid form and reacted with the halo-s-triazines The reaction can also be carried out in suspension in the aqueous solution of alcohols or mercaptans can be.

The compounds of the formula I can optionally subsequently be converted into their acid addition salts with physiologically compatible inorganic or organic acids in a manner known per se. Examples of these are hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, ßem stinic acid, ". Tartaric acid, citric acid, lactic acid, maleic acid

or fumaric acid in question.

The starting materials of the formula III are cyanuric acid halides, e.g. the cyanuric acid chloride known from the literature, or after the method according to the invention by IT-substituted piperazino and / or substituted amino and / or alkoxy and / or alkylthio groups derivatives of cyanuric acid halides partially or completely substituted by alkoxy and / or alkylthio groups.

The new compounds have valuable pharmacological marriage Properties, they are mainly four to five times more effective as a sedative than known, constitutionally similar compounds; they also have a spasmolytic effect; in addition, those compounds that have a free or alkyl substitution

009824/1945

BATH ORIGINAL

te piperidino group, anticonvulsant.

The following examples are intended to explain the invention in more detail:

example 1

2- (4-methylpiperazinyl-1) -4-morpholino-6-piperidino-s-triazirx

55.2 g (0.3 mol) of cyanuric acid chloride are dissolved in 150 ml of hot acetone and the solution is poured into a mixture of 300 g of water and 300 g of ice at 0-5 ° C. with stirring. A fine suspension of cyanuric acid chloride in water is produced. 26.1 g (0.3 mol) of morpholine are dissolved in 30 "ml of acetone and added dropwise with thorough stirring at 0 C. A solution of 5.9 g (0.15 mol) of sodium carbonate in 105 ml is then added at 0 C. The precipitate is filtered off with suction, washed with ice water and then slurried in 600 ml of water. 52 g (0.6 mol) of piperidine are quickly added to this slurry with stirring and ice cooling. The suspension turns slightly yellow. It is warmed to 45 ° C. and stirred for 30 minutes. The mixture is cooled with ice, sucked in and the residue washed with water - Dried 8O ⁰ C and recrystallized from methanol. Melting point: HO - H2 ° C.
Yield: 76 g (90 ^ of theory)
Calculated: C "50.83 f ° H 6.40 # N 24.80 $" Found: C 51.00 $ H 6.52 ^c ß> H 25.10 <fo

* 8g (0.064 mole) of 2-chloro-4-morpholino-6-piperidino-s-triazine with 19.2 g (0.096 koi) - 1-methylpiperazine is heated for 2 hours at 100 ⁰ C. The white-yellow reaction mixture is triturated with AYasser, filtered off with suction, and the residue is washed with water and dried. Melting point: 138-141 ⁰ C.. Aurs yield: 18.2 g ($ 82 of theory)
Calculated: C 58.78 $ H. 8.42 # N 28.18 fo Found: C 59.00 f> H 8.37 & U 27.95 f °

BATH ORIGINAL

009824/19 45

Example 2.

2, ί- DimoFpholino-6- (4-ethylpipera.zinyl-1) -s-triazine

ν g (0.039 mol) of 2-Ghlor-4, o-dimorpholino-s-triazine are dissolved in 150 ml of 1-Methylpipe.razin with gentle heating and heated for 2 hours at TOO to 12O ⁰ C. The excess 1-Uethylpiperp.zin is distilled off in vacuo, the residue triturated with water and extracted with ether. The ether solution is dried with sodium sulfate and the ether is distilled off. The residue is recrystallized from acetone. Melting point: 193-200 ⁰ G. Yield: 12.5 g (92 fi of theory)
Calculated: C 55.00 # H 7.30 # 3Γ 28.00 fo Found: G 55.30 # H 7.98 % ff $ 28.05>

Example 3
2- (4-methylpiperazinyl-i) -4,6-dipiperidino-s-triazine

11 g (0.039 koi) of 2-chloro-4,6-dipiperidino-s-triazine with 150 ml of 1-üethylpiperazin 2 hours at 100 - 120 ⁰ C heated. It was worked up further as in Example 2. Melting point: 120-122 ⁰ C.

Yield: 10.5 g (7.8 # of theory)

Calculated: C 62.58 # H 9.04 #

Found: . C $ 62.10 5ί Η $ 8.99>

Example 4

2-Allylamino-4 -; (4-methylpiperazinyl ~ 1) -6-morpholino-s-triazine

5.1 g (0.02 mol) of 2-allylamino-4-chloro-6-morpholino-s-triazine ■ are slurried in 30 ml of dioxane and 4 g (0.04 mol) 1-methylpiperazine was added. After a short time everything is resolved. It is heated for 1 hour at 100 ⁰ C, whereby the hydrochloride of 1-methyl piperazine precipitates!. Most of the dioxane is distilled off in vacuo, and the residue is triturated with water and extracted with ether. The ether extract is dried with magnesium sulfate

00982A / 19A5

BAD ORiGJNAL

and evaporated. He? remains a tough residue. The residue is dissolved in 2 N ^{r 3:} iiz äure geiört, the solution is treated with activated carbon and filtered?. The base is released from the filtrate with ammonia and etherified. After drying and evaporation of the ether, a light, viscous residue remains, which is chromatographically uniform.

Yield: 5.5 g (£ 86 of theory)
Calculated: C 56.41 # H 7.88 # Ii 30.68 # Found: C 56.20 $ H 8.00 JS N $ 30.90

Example 5

2-Isopropyla nino-4 - (4-methyl piper ^Q .zinyl ~ i) -6-morpholino ^<5-triazine

The implementation and work-up were carried out in Example 4. A white syrupy substance is created.

Yield: 5 _t 3 g ($ 82.5 of theory)
Calculated: C £ 56.02 H 5.46 "5 X 30.50 f" Found: C $ 56.05 H £ 8.52 N 30.35 55.

Example 6

23 g (0, *: WOI) of 2-chloro-4,6-bis-isopropylamino-s-tri ⁱ \ 2in is in "00 ml Dioxon zusamnien with: 22 g (0.22 IZoI) 1-: iethylpiper ?. iin "/ ?. Heated to / OO ⁰ C hour. The dioxane is distilled off and the residue is boiled several times with ether. Dor on evaporation of the remaining residue is i.thers ralzsäure 2n-in dissolved, the Icpun5 mi ^- behsndelt activated charcoal and filtered. There? The filtrate is made alkaline with ammonia and then ethersed out. IAfter drying and evaporation? Ether remains a residue, the r-.u? etrolether is recrystallized. Melting point: 13 ¹ - ¹ 33 G. Yield: 26 "g ( $ 90 of theory)
3ereehnst: C 57.31 % H 9.28 5? N 33.42? S. Found: C 57, cO ^ H 9.36 £ X 33, ^ 0? S

BATH ORIGINAL

009824/1945

Example 7

2,4-Bip- (diethylamino) -6 - (. 4-methylpiperazinyl-1) -s-triazin

20 g (0.0775 mol) of 2-chloro-4,6-bis (diethylamino) -s-triazine is refluxed with 17.0 g (0.17 mol) of 1-methylpiperazine and 80 ml of dioxane for 1/2 hour heated. The dioxane is distilled off and the residue is extracted with ether. The ethereal solution is washed with a little water, dried and evaporated. The residue crystallizes on prolonged standing. The crude product is recrystallized from petroleum ether. Melting point: 75-.76 ^° C.
Yield: 21 g (84 % of theory)

Example 8

2-methoxy-4- (4-methylpiperazinyl-1) -6-morpholino-s-triazine

23.5 g (0.1 mol) of 2,4-dichloro-6-morpholino-s-triazine are suspended in 200 ml of water and with stirring and ice-cooling at 0 - 1O ⁰ C with 10.1 g (0.1 mole ) 1-methylpiperazine, dissolved in 15 ml of water, added dropwise. The mixture is then stirred for 15 minutes without cooling, heated to 30 ° C. and the Pu value is brought to 8 with about 45 ml of 2N sodium hydroxide solution. It is heated to 45 ° C. for 1/2 hour, then cooled with ice and filtered off with suction. 2-chloro-4- (4-methylpiperazinyl-1) -6-morpholino-s-triazine is formed. Melting point: 119-122 ⁰ C (crude product).

12 g (0.04 mol) of 2-chloro-4- (4-methylpiperazinyl-1) -6-mprpholinos-triazine are mixed in 25 ml of methanol with 25 ml of a methanolic sodium methylate solution (0.04 mol) and refluxed for 2 hours cooked. The sodium chloride is filtered off with suction and evaporated. When triturated with water, the residue crystallizes after some time. Melting point: 83-85 ⁰ C. Yield: 8.5 g (72 <fo of theory)
Calculated: C 53.04% H 7.53 # N $ 28.55> Found: C 53.30 $ H 7.76 # N 28.55 % '.

BATH ORIGINAL 009824/1945

2-Stho :: y-4 .- (4-ynethylpiperazirxyl-1) -6-

Example 9 is carried out as in Example 8; the reaction of 2-3hlor-4- ( ⁴ -methylpiperazinyl-1) -6-morpholino-s-tri5.ziri3 was carried out with ethanolic sodium ethylate. Melting point: 96-97 ⁰ C. Yield: 75 i ° of theory
Calculated: X 27.25 7 ° '

Found: H $ 27.50

Example 10

2-Allyloxy-4- (4-methylpiperazinyl-1) -6-morpholino-s-triazine

Example 10 was like Example 8 with allyl alcohol "or its Alcohol- carried out.

Boiling point: 0.01 mm Hg 130 - 165 ° C. Yield: 60 ? ° of theory

Example 11

2, 4-dimorpholino-6- (4-methylpiperazinyl-1) -8-triazine ·

12.4 g (0.04 mol) of 6-Äthylmercapto-2,4-dimorpholino-s-triazine with 10 g (0.1 mol) of 1-JvIethylpiperazin heated for 8 hours in an autoclave at 160 ⁰ C. Most of the excess T-SIe thylpipe ras ins is removed from the mixture in vacuo, rubbed with water / water, filtered off with suction and washed with water. After drying, the preparation is recrystallized from acetone. Melting point: 198 - 200 ⁰ C. ■ ·
Yield: 10.4 g (75 / £ of theory)

Example 12

2-r £ ethoxy-4- (4-meth '/ lpiperazinyl-1) -6-morpholino-s-triazine

21.4 g (0, VMoI) 2 ^ -Dimethüxy-ö-morpholinb-s-triazine are in

009824/1945 ■ bad or.g.nal

Suspended 100 ml of water, added 10 g (0.1 mol) of 1-methylpiperazine and ^{heated to 100 °} C. for 5 hours. The reaction mixture is evaporated to half in vacuo. The resulting oil crystallizes when left standing in the refrigerator for a long time. The • slightly soft crystals are suctioned off and washed with water. After drying at 30 ⁰ C in a vacuum oven, the preparation is recrystallized from petroleum ether. Melting point: 82-84 ⁰ C

Yield: 20 g (68 # of theory)

According to Examples 1-12, the following compounds were also prepared:

a) 2,4-bis (allyloxy) -6- (4-methylpiperazinyl-i) -s-triazine \>) 2- (4-methylpiperazinyl-1) -4-morpholino-6- (pyrrolidino) -triazine, F. = 129 - '31 ⁰ C

c) 2- (hexahydroazepinyl-1) -4 - (- 4-methylpiperazinyl-1) -6-morpholino-s-triazine

d) 2- (4-methylpiperazinyl-1) -4-morpholino-'6- (1,2,3 »6-tetrahydropyridino) -s-triazine, P. = 128-130 ⁰ C.

e) 2- (4-methylpiperazinyl-1) -4- (2-methylpiperidino) -6-morpholinos-triazine

f) 2- (4-methylpiperazinyl-1) -4- (3-methylpiperidino) -6-morpholinos-triazine, P. = 128 - 129 ° C

g) 2- & methylpiperazinyl-1) -4- (4-methylpiperidino) -6-morpholino-

s-triazine
h) 2- (2,6-Dimethylpiperidino) -4- (4-methylpiperazinyl-1) -6-

morpholino-s-triazine
i) 2- (2,6-Dimethylmorpholino) -4- (4-methylpiperazinyl-1) -6-morpho-

lino-s-triazine /

j) 2- (3-Hydroxypiperidino) -4- (4-methylpiperazinyl-1) -6-morpholi-

no-s-triazine, m.p. = 182-185 ° C
k) 2-dimethylamino-4- (4-methylpiperazinyl-1) -6-morpholino-s-tri-, azine

1) 2n -Butylamino-4- (4-methylpiperazinyl-1) -6-morpholino-s-triazine m) 2- (3-methoxypropylamino) -4- (4-methylpiperazinyl-1) -6-morpho- lino-s-triazine

0 0 9 8 2 4/1945 BAD original

η) 2-Cyclohexylamino-4- (4-methylpiperazinyl-.i) -6-morpholino-striazine

ο) 2-Benzylamino-4- (4-methylpiperazinyl-1 ·) -6-morpholino-s-triazine ρ) 2- (2-Diethylamino-ethylamino) -4- (4-methylpiperazinyl-1) -6-morpholino-s-triazine

q) 2-Anilino-4- (4-methylpiperazinyl-1) -6-morpholino-s-triazine r) 2- (4-Toluidino) -4- (4-methylpiperazinyl-1) -6-morpholino-s-

triazine
β) 2- (4-chloroanilino) -4- (4-methylpiperazinyl-1) -6-morpholino-s- ·

triazine
t) 2-furfuryl-methyl-amino-4- (4-methylpiperazinyl-1) -6-morpholino-

"s-triar.in
u) 2-Diethanolamino-4- (4-methylpiperazinyl-i) -6-morpholino-s-tri-

azin
v) 2- (2-morpholino-ethoxy) -4- (4-methylpiperazinyl-1) -6-morpholi-

no-s-triazine., bp _{OfO01 Hg} = ^{194-196 0} C w) 2-ethylmercapto-4- (4-methylpiperazinyl-1) -6-morpholino-s-triazine

x) 2- (4-Ethylpiperazinyl-1) ^ - morpholino-o-piperidino-s-triazine y) 2-Cyclohexyloxy-4- (4-methylpiperaziny1-1) -6-piperidino-s-

triazine
z) 2- (4-Methylpiperaziny 1-1) -4-InOrPhOUnO-O- (2-morpholino-ethoxy) -s-triazine, bp _{Q Q01} = 194 - 196 ⁰ C.

aa) 2-Korpholino-4-piperidino-6- (4-N-propylpiperazinyl-1) -s-

triazine, m.p .: HO - HI ⁰ C
■ fc>"b) 2- (2,6-Dimethylmorpholino) -4 4-methylpiperazinyl-1) -6-piperi-

dino-s-triazine, m.p .: 122-124 ⁰ C cc) 2- (4-allylpiperazinyl-1) -4-morpholino-6-piperidino-s-triazine,

Mp .: 129 to 131 ⁰ C
dd) 2- (2-Ethylpiperidino) 4- (4-methylpiperaziny1-1) -6-morpholinos-triazine

Resinous cash register; not distillable.

Bex .: C 60.78 H 8.86 N 26.10

Found: 60.70 8.80 25.50
.ee) 2-Äthylanino-4- (4-methylpiperazinyl-1) -6-morpholino-s-triazine, m.p .: 107-108 ⁰ C.

00982 W1 945 BAD original

ff) 2- (2, D-Diir.e thylmorpholino) -4- (2,6-dimethylpiperidino) -6- (4-7! iethyipiperazinyi-1) -s-triazine
Resinous! .Lasse; Thin layer chromatogram on AlpO. ,, Benzene / Acetone 6: 1, R ^. = 0.8 Calculated: C 62.42 H 9.24 K 24.35 Found: 61.50. 9.22 23.70

The compounds prepared according to Examples 1-12 can be used in the usual pharmaceutical preparations for pharmaceutical use be incorporated. The following examples describe the production of such pharmaceutical application forms, the single dose for adults is 10-50 mg, for children half of this dose, daily dose for adults: 100-500 mg.

3example 13

Tablets with 40 rr.g 2- (4-methylpiperazinyl-1) -4-morpholino-6- piperiäino-s-triazine

Assertion; ^r : 1 tablet contains: 2- (4 -? '- ethylpiperazinyi-2) -4-morpholino-6-piperidino-s-triazine

40.0 mg

Calcium phosphate secondary 133 »O mg

Potato starch 65.0 mg

Polyvinylpyrrolidone '10.0 mg

Magnesium stearate 2.0 mg

250.0 mg

Production method:

The mixture of the active substance with calcium phosphate and potato starch is granulated with a 20% solution of polyvinylpyrrolidone in ethanol through a sieve of 1.5 mm mesh size, dried at 45 ° C. and rubbed through the above sieve. The granulate obtained in this way is mixed with magnesium te ar at, which has been granulated beforehand by means of a sieve with a mesh size of 1 mm, and pressed into tablets with a 9inra punch. Tablet weight: 250 mg
Daily dose for adults: 100 - 500 mg, half for children.

009824/194 5

ßAD ORIGINAL

Example H

Dragees containing 40 mg of 2- (4-methylpiper.azinyl-1) -4-iaorpholino-6-pi peridino-s-triazine

J) i * j tablets produced according to Example 13 are known in " Way covered with a shell, which consists essentially of sugar and talc. The finished coated tablets are made with the help of Beeswax polished. . -

Dragee weight: 350 mg ~

Example 15

Ampoules containing 10 mg of 2- (4-methylpiperazinyl-1) -4-morpholino-6- piperidino-s-triazine

1 ampoule contains:

2- (4-methylpiperazinyl-1) -4-morpholino-6-piperidino-s-triazine

10.0 mg

n / 10-HCl ad pH 3 »0 approx. 0.35 ml

least. Water to 2.0 ml

Production method;

About half of the required amount of water is heated to 80 C,

added the hydrochloric acid and then dissolved the active ingredient with stirring. After cooling to room temperature, it is made up to the given volume and filtered aseptically with a suitable filter. The solution is packaged in white 2ml ampoules, sterilized die.20 minutes at 120 ⁰ C and then heat-sealed. -

Example 16

Suppositories for adults with 40 mg 2- (4-methylpiperazinyl- 1) ~ 4-morpholino-6-piperidino-s-triazine 1 suppository contains:

2- (4-methylpiperazinyl-1) -4-morpholino-6-piperidino-s-triazine

40.0 mg

0 0 9 8 24/1945 bad original

-H-

Suppository ^{mass (e.g. 7r r} itepsol Y / 45) 1660.0 mg

1700.0 mg

rle rs position procedure:

The finely powdered active ingredient is stirred into the melted suppository mass at 40 C, homogenized and poured into slightly pre-cooled molds.
Suppository weight: 1.7 g. .

Example 17

Child suppositories with 20 mg 2- (4-methylpiperazinyl-1) -4-aiorpho ~ lino-6-piperidino-s-triazine

1 suppository contains:

2- (4-i * i-ethylpiperazinyl-1) -4-morpholino-6-piperidino-s-triazine

20.0 mg

Suppository mass (e.g. Y / itepsol W 45) 980.0 mg

1000.0 mg

Manufacturing process as in Example 16. Suppository weight: 1.0 g.

ORiG / _NAL

009824 / 19AS

Claims (12)

P_a_t_e_n_t_a_n_s_p_r_ü_c_h_o 1. Process for the production of new basic substituted s-trizines of the general formula in which the radical R is a lower alkyl group, which is still by a "basic remainder of the formula may be substituted, an alkenyl, alkylthioalkyl, alkoxyalkyl, aralkyl, aryl, carbalkoxy, lower acyl or aroyl group, and the radicals R / and R ^ * d-ie know to be the same or different , Alky! Mercapto groups with up to 6 carbon atoms or saturated or unsaturated, branched or unbranched alkoxy groups with up to 6 carbon atoms, which can be substituted by a basic radical of the formula II, or basic radicals of the formula II, in which the radicals R, and R., which can be the same or different, unbranched or branched alkyl radicals up to TO carbon atoms, which can optionally be substituted by lower alkoxy, alkylthio or cono or dialkylamino groups, alkenyl radicals, .aralkyl radicals, aryl radicals, the optionally on the aromatic by hydroxyl, alkoxy .009824 / 1945 _BA0 or lower Alleylgrupp.en or substituted by halogen atoms, or mean cycloalkyl radicals, where the radical IU can also be a hydrogen atom and where R, and R. together with the nitrogen atom can also form a heterocyclic 4- to 7-membered ring, the interrupted by an oxygen atom and substituted by lower alkyl, hydroxy or aralkyl groups and their acid addition salts, characterized in that compounds of the formula in which the radicals A ₁ , Ap, A mean halogen atoms and / or alkyl mercapto and / or alkoxy groups, with one mole or a slight excess of a piperazine of the formula IH in which the radical R has the meanings mentioned at the outset, and optionally with 1-2 mol or a slight excess of one or two amines of the formula H-N, in which the radicals R, and R ^ have the meanings mentioned at the beginning, and / or if A ₁ and / or A _{2 are} a halogen atom, with compounds of the formula H ₁ H and R ₂ H, where R ₁ and R _{2 are} the may be the same or different, have the meanings mentioned at the beginning except that of a basic radical of the formula II, given 009824/194 5 ^BA0 if necessary, in stages, and the compounds obtained, if appropriate subsequently converted into their acid addition salts with physiologically compatible acids. 2. The method according to claim 1, characterized · that the reactions be carried out in aqueous suspensions or in organic solvents. 3. The method according to claims 1 to 2, characterized in that that when a halogen atom is exchanged, it is expedient to work in the presence of an acid-binding agent. 4. The method according to claims 1 to 3 »characterized in that the reactions are carried out in a temperature range from about -10 ⁰ C to about +180 C. 5. The method according to claim 1, characterized in that one is used as an acid-binding agent and at the same time as a solvent Excess of the amine to be converted. Used. 6. The method according to claim 1, characterized in that the reaction with volatile compounds of the formula R ^ H and / or RJ3. takes place under pressure. 7. 2- (4-Methylpiperazinyl-1) -4-morpholino-6-piperidino-s-triazine and its acid addition salts. 8. 2,4-Dimorpholino-6- (4-methylpiperazinyl-1) -s-triazine and its Acid addition salts. 9. 2-Allylamino-5- (4-methylpiperazinyl-i) -6-morpholino-s-triazine and its acid addition salts. 10. 2,4-Bis (isopropylamino) -6- (4-methylpiperazinyl-i) -s-triazine and its acid addition salts. 11. 2-Isopropylamino-4- (4-methylpiperazinyl-1) -6-morpholino-s- ■ triazine and its acid addition salts. 0 09 82 4/1945 bad original -ie- 162G528 12. 2- (4- ^ ethylpiperazinyl-1) -4,6-dipiperidino-s-triazine and its acid addition salts. 009824/1945