DE1163840B - Process for the production of hydrazines with effective spinal blocking - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Boarding school Class: C07d

German class: 12 ρ -10/05

Number: 1163 840

File number: C 24588 IV d / 12 ρ

Filing date: July 12, 1961

Opening day: February 27, 1964

The invention relates to a process for the preparation of compounds of the formula

R ₃

N N

and their salts, in which Ri and R2 are replaced by lower Hydrocarbon radicals of aliphatic character, also by heteroatoms, such as oxygen ", nitrogen or sulfur, disubstituted in the aliphatic carbon chain can be interrupted Amino groups and R3 is one by at least one substituted or unsubstituted hydrocarbon radical Aliphatic character is substituted hydrazino group, wherein the hydrocarbon radical also by heteroatoms, such as oxygen, nitrogen or sulfur, in the aliphatic carbon chain can be interrupted.

Lower hydrocarbon residues of aliphatic character are mainly saturated or monounsaturated, alkyl, cycloalkyl or cycloalkylalkyl radicals having at most 8 carbon atoms. By Heteroatoms in the aliphatic carbon chain are mainly interrupted radicals of this type Oxaalkyl, oxaalkylene, azacycloalkyl, azaalkylene or oxacycloalkylalkyl radicals. To be mentioned are in particular Methyl, ethyl, allyl, propyl, isopropyl, straight or branched, connected in any position Butyl, pentyl, hexyl or heptyl radicals, 3-oxabutyl, 3-oxapentyl-, 3-oxaheptyl-, butylene- (1,4) -, Butylene (1.5), hexylene (1.5), hexylene (1.6), hexylene (2.5), heptylene (1.7), heptylene (2, 7) -, heptylene- (2.6) -, 3-oxa- or azapentylene- (1,5) -, 3-methyl-3-azapentylene- ( 1,5) -, 3-oxa- or azahexylene- (l, 6) -, cyclopentenyl-, cyclohexyl-, cyclopentyl- or cyclohexenyl radicals, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenylmethyl or -äthylreste or 2-oxa-cyclopentylmethyl- or 4-azacyclohexyl radicals.

Substituents of these radicals in the case of R3 are above all free hydroxyl groups for alkyl radicals, but especially aryl radicals or heterocyclic radicals, such as phenyl, pyridyl, furyl or thienyl radicals, the aryl or heterocyclyl radicals being lower alkyl radicals, such as methyl, Ethyl, propyl or butyl radicals, lower alkoxy radicals such as methoxy, ethoxy or methylenedioxy, halogen atoms such as chlorine, bromine or trifluoromethyl, nitro or processes for producing spinal blocking
more effective hydrazines

Applicant:

CIBA Aktiengesellschaft, Basel (Switzerland)

Representative:

Dipl.-Ing. E. Splanemann, patent attorney,

Hamburg 36, Neuer Wall 10

Named as inventor:

Dr. Alexander Staehelin,

Dr. Albrecht Hüni, Basel (Switzerland)

Claimed priority:

Switzerland of August 4, 1960 (No. 8838)

Switzerland from October 11, 1960

(No. 11393, No. 11394)

Switzerland of June 19, 1961 (No. 7178)

Can carry amino groups as substituents, while z. B. for cycloalkyl, oxa or azacycloalkyl radicals lower alkyl radicals, such as methyl, come into question. In the aralkyl or heterocyclylalkyl radicals the alkylene radical is primarily a methylene or ethylene radical.

The invention particularly relates to processes for the preparation of compounds of the formulas I and II

R ₃ '

NH - NH - C _n H _2n
ι R ' - R ' I. N- AR ₁ ,
NN / ^l
v- < \
R ₂ ' R ₁ ' C _n H _2n - R ₂ ' N-NH ₂
I. II R ₃ , Λ
\ NN /
Ν— Κ *) - Ν
/ N \ R ₄ / \
/ 409 510/523

and their salts, in which η stands for the numbers 1 or 2, R 'is a pyridyl, furyl or thienyl radical and Ri ', R2', R3 'and R4' are lower alkyl radicals, such as methyl, propyl, isopropyl, butyl, iso or sec-butyl, but especially ethyl or Ri 'and R2' or R3 'and R4' together are a ^ n alkylene, oxa or azaalkylene radical, such as Butylene- (1,4), pentylene- (1,5), 3-oxapentylene- (1,5), 3-azapentylene- (1,5), hexylene- (1,6), 3-azahexylene- (l , 6) or 3-methyl-3-azapentylen- (1,5).

The invention further particularly relates to processes for the preparation of compounds of the formula III and IV

Compounds of the formula NH - NH - (CH ₂ ) * - Py are particularly valuable

N (C ₂ H ₅ ) -

R ₃ '

R ₄ '

NH-ν;

R ₅
R ₆

NN
VA j-N

R ₅

N ~ NH ₂

NN

R -

^Rl

-N

and their salts, in which Ri ', R ₂ ', R3 'and Ri' are lower alkyl radicals such as methyl, propyl, isopropyl, butyl, iso- or sec-butyl, but especially ethyl, or Ri 'and R ₂ ' or R ₃ 'and FU' together represent an alkylene, oxa or azaalkylene radical, such as butylene (1,4), pentylene (1,5), 3-oxapentylene (1,5), 3-azapentylene (1,5 ), Hexylene- (1,6), 3-azahexylene- (l, 6) or 3-methyl-3-azapentylene- (l, 6), and at least one of the radicals R ₅ and R6 is a lower alkyl radical, e.g. B. one of the just mentioned, an oxyalkyl radical with 2 carbon atoms in front of the oxy group, z. B. oxyethyl, or a cycloalkyl or azacycloalkyl radical, e.g. B. cyclopentyl or cyclohexyl, or an oxaalkyl radical, e.g. B. 3-oxabutyl or 3-oxapentyl, and optionally denotes the other hydrogen, or R ₅ and Re together represent one of the alkylene, aza or oxaalkylene radicals just mentioned. In the formulas I to IV, the tertiary amino groups are primarily diethylamino groups.

The new compounds and their salts have valuable pharmacological properties. So they have an inhibitory effect on the transmission of excitation in the central nervous system and can therefore as a remedy, e.g. B. as spinal blockers, in neurological diseases, especially those which are associated with increased spasticity can be used. Also an application in the Veterinary medicine is possible.

N N

and their salts, in which η denotes the numbers 1 or 2 and Py denotes pyridyl, especially pyridyl- (4), especially 2- [pyridyl- (4) -methylhydrazino] -4,6-bis-diethylamino-1 , 3,5-triazine and its salts, and the compounds of the formula

R ₅

NH-N

(C ₂ Hs) ₂ N

and

N N

N - NH ₂

N N

(C ₂ Hs) ₂ N

N (C ₂ Hs) ₂

and their salts, in which R _{5 is} a lower alkyl radical. especially methyl, ethyl, propyl, isopropyl, butyl, isobutyl or sec-butyl, a lower oxyalkyl radical with 2 to 4 carbon atoms in front of the oxy group, especially the β-oxyethyl radical and Re is hydrogen or has the same meaning as R ₅ , and especially the 2- [l '- (/ 3-hydroxyethyl) hydrazino] -4,6-bis-diethylamino-1,3,5-triazine, the 2 - (2', 2 '- dimethylhydrazino) - 4, 6 - diethylamino-1,3,5-triazine and 2- (l'-methylhydrazino) -4,6-bisdiäthylamino-1,3,5-triazine, and their salts.

The new compounds are obtained by methods known per se by a) a Compound of formula

R ₂

N N

'N

where Ri and R _{2 have} the meaning given at the beginning and X is a reactive esterified or etherified oxy group. especially a halogen atom, such as chlorine or bromine, or an aryloxy, such as phenoxy group or a free or etherified mercapto group, especially an alkyl mercapto, such as methyl, ethyl, propyl or butyl mercapto group, or an aralkyl mercapto group, e.g. B. a benzyl mercapto group, is reacted with a hydrazine of the formula R3H, where R3 has the meaning given at the beginning. The reaction is expediently carried out in the presence of diluents, possibly also in the presence of condensers

sation agents, ζ. B. an excess of the hydrazine, carried out, in addition, in the presence of catalysts, such as copper powder, can work. Another embodiment b) of the method consists in using compounds of the formula

NH - NH ₂

N N

where Ri and R2 have the meaning given at the beginning have to introduce an unsubstituted or substituted lower hydrocarbon radical aliphatic Character, which can also be interrupted by heteroatoms in the hydrocarbon chain can, with reactive esters of corresponding alcohols, advantageously in the presence of acid-binding agents Condensing agents, e.g. B. also an excess of the hydrazine compound. As reactive esters, in particular those strongly inorganic or organic are Acids, e.g. B. the hydrohalic acids, z. B. hydrochloric acid, hydrobromic acid, hydriodic acid, Sulfuric acids, organic sulfonic acids, e.g. B. benzenesulfonic acids or alkanesulfonic acids to name.

However, according to the further process variant c), the abovementioned hydrazines can initially also be used with an oxo compound resulting from reduction of a corresponding alcohol, e.g. B. a React aldehyde or ketone aliphatic character and the resulting Schiff base or reduce a similar condensation product. The oxo compound. even in the present of the reducing agent can be used. As a reducing agent are, for. B. catalytically excited Hydrogen, e.g. B. hydrogen in the presence of a noble metal catalyst of the VIII. Group of the. Periodic Systems, e.g. B. platinum oxide, nascent hydrogen or hydrogen donating agents, e.g. B. complex metal hydrides, to be mentioned. Depending on the conditions of the alkylation can one or more residues of aliphatic character enter the hydrazino group.

Finally, the new compounds can also be obtained by following the other Process variant d) in 2-Ri-4-R2-6-Z-1,3,5-triazines, in which Ri and R2 have the meaning given above have and Z is a group R3 substituted by an acyl radical, in which R3 is the has the meaning given above, splits it off. An acyl radical is z. B. an aliphatic or aromatic Carboxylic acid residue, e.g. B. an alkanoyl or benzoyl radical, such as acetyl, trifluoroacetyl or benzoyl radical, or a sulfonic acid residue such as benzene or toluenesulfonic acid residue. The split will carried out in the usual way by hydrolysis, especially acid hydrolysis.

The reactions are in a manner known per se, in the absence or appropriately in the presence of Condensing agents and / or catalysts, carried out at ordinary or at elevated temperature.

Depending on the procedure, the new compounds are obtained in the form of the free bases or theirs Salts. Therapeutically useful salts can be formed from the bases, e.g. B. of hydrohalic acids, Sulfuric acids, phosphoric acids, salpic acid, perchloric acid; aliphatic, alicyclic, aromatic or heterocyclic carboxylic or sulfonic acids, such as formic, acetic, propionic, Oxal, amber, glycol, milk, apple, wine, lemon, ascorbic, oxymalein, dioxymalein or pyruvic acid; Phenyl acetic, benzoin, p-aminobenzoic, anthranil, p-oxybenzoic, salicylic or p-aminosalicylic acid; j methanesulfone, ethanesulfone, Oxyethane sulfonic acid, ethylene sulfonic acid; Toluenesulfonic, naphthalenesulfonic or sulfanilic acid; Methionine, tryptophan, lysine or arginine.

The new compounds or their salts can be used as medicaments, e.g. B. in the form of pharmaceuticals Find preparations that use them or their salts in admixture with one for enteral or pharmaceutical, organic or inorganic, solid or liquid, suitable for parenteral administration Support material included. For the formation of the same, such substances come into question, those with the new Connections not responding, such as B. water, gelatin, lactose, starch, magnesium stearate,

Talc, vegetable oils, benzyl alcohol, gum, polyalkylene glycols, cholesterol or other known ones Drug carrier. The pharmaceutical preparations can e.g. B. as tablets, coated tablets or in liquid Form as solutions, suspensions or emulsions. If necessary, they are sterilized and or or contain auxiliaries such as preservatives, stabilizers, wetting agents or emulsifiers, salts to change the osmotic pressure or buffer. You can also do others therapeutically contain valuable substances. The specimens are obtained using conventional methods. They contain the active ingredient e.g. B. in an amount of 5 to 100 mg per dosage unit. The amount of the carrier material can of course vary within wide limits, but it is useful to contain the new ones Preparations 1 to 60% active ingredient.

Unless the starting materials necessary for carrying out the reactions mentioned are known they can be obtained by the usual methods.

The invention also relates to those embodiments of the method in which one of a compound obtainable as an intermediate at any stage of the process goes out and carries out the missing procedural steps or terminates the procedure at any stage, or forms a starting material under the reaction conditions or is used in the form of a salt.

The invention is described in more detail in the following examples. The temperatures are in degrees Celsius specified.

■ Example 1

15.0 g of 2-chloro-4,6-bis-diethylamino-l, 3,5-triazine and 6.6 g of methylhydrazine are dissolved in 100 cm ^{3 of} ethanol and heated to the boil for 4 hours. The mixture is completely evaporated, the residue dissolved in ether, washed acidic with water and three times with dilute hydrochloric acid. The 6g aqueous, acidic solution is made alkaline with dilute sodium hydroxide solution and extracted several times with ether. The dried ether solution is evaporated completely and the liquid residue in the

1 L63

Distilled under high vacuum. The 2- (1'-methylhydrazino) is obtained in this way - 4,6 - bis - diethylamino -1,3,5-triazine of the formula

CH ₃

N-NH ₂

(C ₂ Hs) ₂ N-

N
JN (QsHs) ₈

IO

as a liquid, bp 0.15 126 to 128 °.

B e i s ρ i el 2

15.0 g of 2-chloro-4,6-bis-diethylamino-l, 3,5-triazine and 8.6 g of 1,1-dimethylhydrazine are dissolved in 100 cm ^{3 of} ethanol and heated to the boil for 4 hours. The mixture is completely evaporated, the residue dissolved in ether, washed acidic with water and three times with dilute hydrochloric acid. The aqueous, acidic solution is made alkaline and extracted several times with ether. The dried ether solution is completely evaporated and the liquid residue is distilled twice in a high vacuum. This gives 2- (2 ', 2'-dimethylhydrazino) -4,6-bis-diethylamino-1,3,5-triazine of the formula

NH-N

(C ₂ Hs) ₂ N

'X

N N

CH ₃

CH ₃

N (C ₂ Hs) ₂

30th

35

40

as a liquid, b.p. ₂ 115 to 116 °.

Example 3

10.0 g of 2-chloro-4,6-bis-diethylamino-l, 3,5-triazine and 7.3 g of ß-hydroxyethylhydrazine are dissolved in 100 cm ^{3 of} ethanol and heated to the boil for 6 hours. The mixture is completely evaporated, the residue dissolved in ether, washed with water and three times with dilute hydrochloric acid. The aqueous, acidic solution is made alkaline with dilute sodium hydroxide solution and extracted several times with ether. The dried ether solution is completely evaporated and the residue is recrystallized three times from petroleum ether. This gives 2- [1 '- (/ I-hydroxyethyl) hydrazino] -4,6-bis-diethylamino-1,3,5-triazine of the formula

H ₂ N - N - CH ₂ - CH ₂ - OH

(C ₂ Hs) ₂ N

N N

N (C ₂ Hs) ₂

55

60 3.4 g of n-butyraldehyde are added, the mixture is left to stand at room temperature for several hours and heated to the boil for a further 2 hours. The solution is concentrated, the oily residue is dissolved in 100 cm ^{3 of} glacial acetic acid and hydrogenated under normal pressure, at room temperature and in the presence of 0.3 g of platinum oxide. The uptake of hydrogen takes place within 1.5 hours. The filtered solution is completely evaporated, the oily residue dissolved in dilute hydrochloric acid, shaken with ether, then the acidic, aqueous solution made alkaline with dilute sodium hydroxide solution and extracted with ether. The dried ether solution is concentrated and the residue is distilled in a high vacuum. This gives 2 - (2 '- η - butylhydrazino) - 4,6 - bis - diethylamino-1,3,5-triazine of the formula

NHNH - CH ₂ - CH ₂ - CH ₂ - CH ₃

-N N

-I JN (C ₂ Hs) ₂

as a viscous oil, bp. _{0, 3155-160} °.

Example 5

20 g of 2-hydrazino-4,6-bis-diethylamino-1,3,5-triazine are ^{mixed with 100 cm 3 of} acetone, left to stand at room temperature for several hours and heated to boiling for a further 1.5 hours. The solution is completely evaporated, the oily residue dissolved in 150 cm ^{3 of} glacial acetic acid and hydrogenated under normal pressure, at room temperature and in the presence of 0.5 g of platinum oxide. The hydrogen uptake takes about 5.5 hours. The filtered solution is concentrated and the oily residue is treated with ethanolic hydrochloric acid. By adding absolute ether and inoculating, the 2- (2'-isopropylhydrazino) -4,6-bis-diethylamino-1,3,5-triazine dihydrochloride of the formula crystallizes

CH ₃

NHNH - CH

2HCl

CH ₂

in white crystals that melt at 63 to 65 °.

Example 4

12.0 g of 2-hydrazino-4,6-bis-diethylamino-1,3,5-triazine are dissolved in 100 cm ^{3 of} absolute ethanol with NN
(C ₂ Hs) ₂ N -AJ- N (C ₂ Hs) ₂

the end; white crystals, F. 190 I is 193 ".

Example 6

12.0 g of 2-hydrazino-4,6-bis-diethylamino-1,3,5-triazine are mixed in 100 cm ^{3 of} absolute ethanol with 4.0 g of cyclopentanone, left to stand at room temperature for several hours and heated to the boil for a further 2 hours . The solution is completely evaporated, the oily residue dissolved in 100 cm ^{3 of} glacial acetic acid and hydrogenated under normal pressure, at room temperature and in the presence of 0.5 g of platinum oxide. The uptake of hydrogen takes place within about 11 hours. The filtered solution is concentrated and the oily residue is distilled in a high vacuum.

This gives 2- (2'-cyclopentylhydrazino) -4,6-bis-diethylamino-1,3,5-triazine the formula

NH-NH

NN
(C ₂ Hs) ₂ N -1 [^

as a thick oil, boiling point 0.35 165 to 167 °.

Example 7

30.0 g of 2-hydrazino-4,6-bis-diethylamino-1,3,5-triazine are mixed with 11.6 g of cyclohexanone ^{in 200 cm 3 of absolute ethanol.} The mixture is left to stand at room temperature for several hours, then heated to boiling for a further 2 hours and then the solvent is completely evaporated off. 25 g of crude cyclohexylhydrazone are dissolved from the oily residue in 150 cm ^{3 of} glacial acetic acid, and the mixture is hydrogenated under normal pressure at room temperature and in the presence of 0.5 g of platinum oxide. The hydrogen uptake takes place within about 2 hours. The filtered solution is evaporated completely, the residue is dissolved in chloroform and the solution is washed with dilute sodium hydroxide solution. The dried chloroform solution is concentrated and the viscous residue is mixed with ethanolic hydrochloric acid. By adding absolute ether, the 2- (2'-cyclohexylhydrazino) -4,6 - bis - diethylamino -1,3,5-triazine - dihydrochloride of the formula crystallizes

NHNH

N N

2HCl

(C ₂ Hs) ₂ N-

N (C ₂ Hs) ₂

35

40

the end; white crystals, m.p. 183 to 185 °.
Example 8

30 g of 2-hydrazino-4,6-bis-diethylamino-1,3,5-triazine are mixed ^{with 13.4 g of N-methyl-4-piperidone in 100 cm 3 of} absolute alcohol, the mixture is left to stand at room temperature for several hours and heated to boiling for another 2 hours. The solution is completely evaporated; 10.7 g of hydrazone are dissolved from the oily residue in 100 cm ^{3 of} glacial acetic acid and hydrogenated under normal pressure, at room temperature and in the presence of 0.5 g of platinum oxide. The uptake of hydrogen takes place within 1.5 hours. The filtered solution is concentrated, the residue is dissolved in chloroform and washed alkaline with dilute sodium hydroxide solution. The dried chloroform solution is completely evaporated and the residue is distilled in a high vacuum. The 2- [2'-N'-methylpiperidyl- (4) hydrazino] -4,6-bis-diethylamino-1,3 "5-triazine of the formula is obtained in this way

NHNH

N-CH ₃

N N

(C ₂ Hg) ₂ N -H _n ^ "N (C ₂ Hs) ₂
as a viscous liquid, boiling point 0.3 190 to 192 °.

Example 9

12.0 g of 2-hydrazino-4,6-bis-diethylamino-1,3,5-triazine are dissolved in 100 cm ^{3 of} ethanol and mixed with 3.42 g of methyl ethyl ketone. The mixture is left to stand for several hours at room temperature, then heated to boiling for 2 hours and concentrated. The remaining viscous hydrazone is dissolved in 100 cm ^{3 of} glacial acetic acid and hydrogenated under normal pressure, at room temperature, in the presence of 0.3 g of platinum oxide. The hydrogen uptake takes place within 9 hours. The filtered solution is completely evaporated, the residue is mixed with water, acidified with 2η hydrochloric acid and shaken through with ether. The acidic, aqueous solution is made strongly alkaline and extracted again with ether. The dried ether solution is concentrated and the residue is distilled in a high vacuum. The 2 - (2 '- sec-butylhydrazino) - 4,6 - bis - diethylamino-1,3,5-triazine of the formula is obtained in this way

60 CH ₃

NH-NH-CH

CH ₂ CH ₃

N N

(C ₂ Hs) ₂ N -IJ- N (C ₂ Hs) ₂

as a viscous oil, boiling point 0.3 158 to 160 °.
Example 10

5.1 g of 4-pyridine aldehyde are added to 12.0 g of 2-hydrazino-4,6-bis-diethylamino-1,3,5-triazine in 100 cm ^{3 of} absolute ethanol, the mixture is left to stand at room temperature for several hours and 2 Heated to the boil for hours. The solution is completely evaporated, the crystallized residue is dissolved in 100 cm ^{3 of} glacial acetic acid and hydrogenated under normal pressure, at room temperature and in the presence of 0.5 g of platinum oxide. The hydrogen uptake takes place within 4.5 hours. The filtered solution is concentrated, the dark, oily residue is dissolved in 2η hydrochloric acid, filtered through activated charcoal, made alkaline with 2η sodium hydroxide solution and extracted with ether. The dried ether solution is evaporated completely, the oily residue is dissolved in ethyl acetate, acidified with ethanolic hydrochloric acid and cooled. The crystallized product is suction filtered and recrystallized from a mixture of ethyl acetate, absolute alcohol and ether. The 2- [2'-pyridyl- (4 ") - methylhydrazino] -4,6 - bis - diethylamino -1,3,5 - triazine dihydrochloride of the formula is obtained in this way

NHNH - CH ₂

65 (C ₂ Hs) ₂ N NN
A _x JN (C ₂ Hs) ₂

2HCl

in white crystals that melt at 231 to 235 °.

409 510/523

Example 11

20 g of 2-chloro-4-diethylamino-6-pyrrolidino-1,3,5-triazine and 9.0 g of methylhydrazine are dissolved in 150 cm ^{3 of} alcohol and heated to the boil ^{for 4 x} _{1/2 hours.} The work-up is carried out as in Example 1. The liquid residue is distilled in a high vacuum. This gives 2- (1'-methylhydrazino) -4-diethylamino-6-pyrrolidino-1,3,5-triazine of the formula

CH ₃

N-NH ₂ hydrazino) - 4- diethylamino - 6 - pyrrolidino - 1,3,5-triazine of the formula

NHNH

N N

10 N-

N (C ₂ Ha) ₂

N N

N-

N (C ₂ Hs) ₂

as a liquid, Kp.o, o? 119 to 121 °.

The 2-chloro-4-diethylamino-6-pyrrolidino-1,3,5-triazine used as starting material is obtained as follows:

42 g of 2,4-dichloro-6-diethylamino-1,3,5-triazine (JT Thurst ο η and coworkers, J. Am. Chem. Soc, 73, p. 2981 [1957]) are in 250 cm ³ Dissolved benzene and treated with a solution of 27 g of pyrrolidine in 100 cm ^{3 of benzene at room temperature.} The internal temperature rises slightly and the pyrrolidine hydrochloride precipitates out as an oily product. After standing for 1 hour at room temperature, the mixture is filtered through activated charcoal and concentrated, and the residue is extracted with hot petroleum ether. The extract is filtered again through activated charcoal, the extractant is evaporated and the pale yellow residue, consisting of 2-chloro-4-diethylamino-6-pyrrolidino-1,3,5-triazine, is recrystallized in methanol; white prisms, F. 90 to 91 °.

Example 12

15 g of 2-hydrazino-4-diethylamino-6-pyrrolidino-1,3,5-triazine, described in patent application C 24587 IVd / 12p, are ^{mixed with 5.9 g of cyclohexanone in 100 cm 3 of} absolute alcohol, several at room temperature Left to stand for hours and heated to boiling for a further 2 hours. The solution is completely evaporated, the oily residue dissolved in 120 cm ^{3 of} glacial acetic acid and hydrogenated under normal pressure, at room temperature and in the presence of 0.4 g of platinum oxide. The hydrogen uptake takes place within about an hour and 20 minutes. The filtered solution is concentrated and the residue is dissolved in chloroform. The chloroform solution is washed with dilute sodium hydroxide solution and with water, dried, filtered and evaporated. The residue is dissolved in warm ethyl acetate, an alcoholic hydrochloric acid solution and absolute ether are added, the mixture is cooled and the hydrochloride formed is suction filtered. This salt is then dissolved in water, made alkaline with dilute sodium hydroxide solution and extracted several times with ether. The dried ether solution is evaporated and the residue is recrystallized from petroleum ether. The 2- (2'-cyclohexylin-white crystals which melt at 113 ° to 114 ° are obtained in this way.

Example 13

15 g of 2-hydrazino-4-diethylamino-6-pyrrolidino-1,3,5-triazine are ^{mixed with 6.4 g of 4-pyridine aldehyde in 100 cm 3 of} absolute alcohol, left to stand at room temperature for several hours and then heated to the boil for 2 hours . The solution is completely evaporated and the crystallized residue is dissolved in 120 cm ^{3 of} glacial acetic acid and hydrogenated under normal pressure, at room temperature and in the presence of 0.4 g of platinum oxide. The hydrogen uptake takes place within about 5 hours. The filtered solution is evaporated completely, the residue is dissolved in dilute hydrochloric acid and filtered. The acidic, aqueous solution is then made alkaline and extracted several times with ether. The dried ethereal solution is completely evaporated, the oily residue is dissolved in warm ethyl acetate and an alcoholic hydrochloric acid solution and absolute ether are added. The dihydrochloride crystallizes from the cooled solution and is recrystallized from absolute alcohol — absolute ether. The 2- {2 '- [pyridyl- (4 ") - methyl] hydrazino} -4-diethylamino-6-pyrrolidino-1,3,5-triazine dihydrochloride of the formula is obtained in this way

NHNH - CH ₂

N N

2HCl

N (C ₂ Hs) ₂

in white crystals that melt at 237 to 240 °.

Claims (1)

Claim: Process for the production of spinal blocking hydrazines, characterized in that that one in a known manner a) a compound of the formula N N where Ri and R ₂ are disubstituted amino groups by lower hydrocarbon radicals of aliphatic character, which can also be interrupted by heteroatoms in the aliphatic carbon chain, and X is a reactive esterified or etherified oxy group or is a free or etherified mercapto group, preferably a halogen atom, is reacted with a hydrazine of the formula R3H, where R3 is a hydrazino group substituted by at least one substituted or unsubstituted hydrocarbon radical of aliphatic character, the hydrocarbon radical also being interrupted by heteroatoms in the aliphatic carbon chain, or
b) compounds of the formula NH - NH ₂ N N where Ri and R2 have the meaning given above have, with a reactive ester one substituted or unsubstituted alkanol, which also has heteroatoms in the carbon chain can be interrupted, implements or c) said hydrazinotriazine with a substituted or unsubstituted one by reduction Alkanol, which can also be interrupted by heteroatoms in the carbon chain, resulting oxo compound and the resulting condensation product is reduced or d) in 2-Ri-4-R ₂ -6-Zl, 3,5-triazines, in which Ri and R2 have the meaning given above and Z is a group R3 substituted by an acyl radical, in which R3 has the meaning given above, splitting off these and, if desired, converting the free bases obtained into their salts or the salts obtained into the free bases. Considered publications:
German interpretative document No. 1018 424. When the registration was announced, three pages of the test report were laid out.