LU81704A1 - METHOD FOR THE PRODUCTION OF 1,2,3-THIADIAZOL-5-YL-UREAS - Google Patents

Description

• ’- SCHERINGAG

Intellectual Property

Berlin, 13 · 06.1979; METHOD FOR PRODUCING 1,2,3-THIADIAZOLE

! 5-YL-UREA SUBSTANCES

j | ! The invention relates to a new process for the preparation of 1,2,3-thiadiazol-5-yl-ureas.

j Process for the production of ureas of the designated

Kind are already known (DE-OS 22 1¾632, DE-OS 26 3β 99 *) · These methods use 5-amino-l, 2,3-thiadiazole as a starting material, a substance that is not easily accessible and not entirely is harmless.

The object of the present invention is to create a process which allows a technically simple and safe production of 1,2,3-thiadiazole-p "j, yl-ureas.

i f i S This object is achieved according to the invention by a method for

Production of 1,2,3-thiadiazol-5-yl-ureas of the general formula N-CH R, II II / 1

N C -NH-CO-N ^ I

2 i 'solved in the i - 2 - / φ * 0>

CO

? * '$ ^ | 2 Board: Dr. Herbert Asmls Dr. Christian Bruhn * Hans-Jörgen Hamann Postal address: SCHERING AG * D-1 3! In 65 * PO box £ 5 0311 I? Dr. Heinz HannseKart Otto MittelstenscheidDr. Horst Witzei t «· a-.r, uai ^ hi mninmn

SCHERING AG

Commercial legal protection R ^ hydrogen or optionally one or more alkyl interrupted by oxygen or sulfur atoms, an alkyl optionally interrupted one or more times by oxygen or sulfur atoms, an optionally mono- or polysubstituted by alkyl cycloaliphatic hydrocarbon residue, an optionally mono- or aromatic hydrocarbyl radical substituted by alkyl and / or halogen and / or alkylthio and / or alkoxy and / or trifluoromethyl and / or the nitro group, an optionally substituted heterocyclic hydrocarbon containing at least one N atom or R ^ and Rg üeKieinsi niit ^ em N-Atora represent the Morpholino-, Piperidino- or Pyrrolidino group, and which is characterized in that a 1,2,3-thiadiazole-5-carboxylic acid azide of the formula

N-CH

II II

N C-CO-N "II

\ / 3 with an amine of the general formula - 3 - / 0> m ^ Board: Dr. Herbert Asmis Dr. Christian Bruhn * Hans-Jürgen Hamann Postal address: SCHERÏNG AG - 0-1 Berlin 65 - P.O.Box 65 0311

; '' - SCHERING AG

^ Intellectual Property Rights i! λ

i H - N "XU

j.

dissolved in an inert organic solvent and the reaction product in known per se Manner isolated, where R_ and R have the meaning given above.

The radicals designated in the general formula I are to be understood in particular those in which R ^ is hydrogen or C ^ -C ^ alkyl, for example methyl, ethyl, propyl, isopropyl or butyl, R0 C ^ -C ^ alkyl , first

Example methyl, ethyl, propyl, isopropyl or butyl, C -Cp-cycloalkyl, for example cyclopentyl or cyclo-5o hexyl, methyl-C ^ -Co-cycloalkyl, for example methyl-cyclohexyl, phenyl, halophenyl, for example 4- Chloro-j, j phenyl, C ^ -C ^ alkylphenyl, for example 4-methylplienyl, * C ^ -C ^ alkoxyphenyl, for example 4-methoxyphenyl, nitrophenyl, trifluoromethylphenyl, pyridyl or pyrimidyl mean.

I Special embodiments of the process according to the invention consist in that the reaction at temperatures of 20 ° to 180 ° C., 1 1 -4 - i r.

CS

Approx

CO

j £ Board: Dr. Herbert Asmis pr. Christian BruhnHans-Jürgen Hamann Postal address: SCHERING AGD-1 Berlin 65Pox 65 0311

. 4th SCHERING AG

Commercial legal protection, preferably from 50 ° to 120 ° C, is carried out that the reaction is carried out at the boiling point of the reaction mixture, that equimolar amounts of the azide of the formula II and the amine of the general formula III are used, that the reaction of the Azide of the formula II with the amine of the general formula III takes place in one step and that a 1,2,3-thiadiazole-5-carboxylic acid azide of the formula II is used, which is prepared by processes known per se and from the reaction mixtures obtained is not isolated, so that a continuous procedure is also made possible.

The 1,2,3-thiadiazole-5-carboxylic acid azide of the formula II can be prepared by the following processes which are already known per se, by a) 1,2,3-thiadiazole-5-carboxylic acid of the formula

N-CH

Î «

N C - C00H IV

with chloroformic acid esters of the general formula

CI - CO - 0R ^ V

in an inert solvent in the presence of acid - 5 - ty

Ci en 03

TT

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Vftrefanrf · Hr Uarh ^ rt £ «m! E. Πρ rkrtellan Onthn. Pane.lfirncn Uamann Pne * an «/ + irift · .QCUPPINft ß. Π.1 Rorlin fiü. DneMapb CCM ΛΛ

'' ·. 5. SCHERING AG

Intellectual Property ! ! | binding agents to the mixed anhydride of the general | a formula j! n_λ cn; |! ! i

i N j-CO-O-CO-OR VI

! S '"" 3 i can react and then with solutions of alkali azides of the general formula

Meli VII

converts or i * b) 1,2,3-Tbiadiazol-5-carboxylic acid halides of the general formula

N_, CH

II!

N jj-CO-X VIII

\ j 'in inert organic solvents with aqueous solutions! gene of alkali azides of the general formula

| MeN ^ VII

i implements or i - 6 -! ’Fr- i ** l \ es ί ti Board: Or. Herbert Asmis - Dr. Christian BruhnHans-Jörgen Hamann Postal address: SCHERING AGD-1 Berlin 65Postbox 650311

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Commercial legal protection c) 1,2,3-thiadiazole-5-carboxylic acid hydrazide of the formula

N_CH

11!

N / -CO-NH-NH ,, XX

\ s / in inert solvents with solutions of alkali nitrites of the general formula

KeN02 X

or with alkyl nitrites of the general formula r3-o-no XI

in the presence of acid to 1,2,3-thiadiazole-5-carboxylic acid azide of the formula

N_CH

II ||

N jpO-N0 II

\ s ^ j, where R ^ is a C ^ -C ^ alkyl radical, Me is a monovalent metal equivalent, preferably a sodium, potassium or lithium atom and X is a halogen atom, preferably a chlorine atom.

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Oil ► CT3

V

T »u Board: Dr. Herbert AsmisDr. Christian BruhnHans-Jörgen Hamann Postal address: SCHERING AG D-1 Berlin 65 * Postfach 65 0311

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Intellectual Property

The azide of the formula II obtainable hereafter advantageously does not need to be isolated from the reaction mixtures obtained, but is used directly for the process according to the invention using these mixtures.

The 1,2,3 ™ thiadiazole-5 “carboxylic acid required as starting products and their derivatives can also be prepared in a manner known per se by, for example, a) acylhydrazones of propionaldehyde of the general formula

H

• I

CH3-CH2-C = N-NH-CO-R ^ XII

with thionyl chloride of the formula

S0C12 XIII

to 5-methyl-l, 2,3-thiadiazole of the formula N_, CH

Ȇ

N ji-CH XIV

’

can react and this then with common oxidizing agents such as chromium (VI) oxide, potassium permanganate and nitric acid to 1,2,3-thiadiazole-5-carboxylic acid of formula IV

- 8th -

\ t L

. CO

«V

T "·: ± Board of Directors: Dr. Herbert Asmis · Dr. Christian Bruhn Hans-Jürgen Hamann Postal address: SCHERING AG · D-1 Berlin 65 · Postfach 65G311

'' - _ 3. SCHERING AG

Intellectual Property

N-, CH

"ll

N «-COOH IV

N, S / oxidizes or b) acylhydrazones of the formyl acetic ester of the general formula H - C - CH - COOR, I ά 3

XV

N-NH-CO-R ^ with thionyl chloride of the formula

soci2 XIII

to 1,2,3-thiadiazole-5 "cari:) oleic acid: rl of the general formula

N_CH

11 1 N »-COOR- XVI.

3 implements. This can then be done with hydrazine of the formula

nh2 - nh2 XVII

optionally in polar organic solvents, to 1,2,3-thiadiazole-5-carboxylic acid hydrazide of the formula - 9 - / i

Cf

Ci m .I Board of Directors · Br. Horhnrt Asmis - Br. Christian Rrnhn · Hans-Jürom Hamann Postal address? SCHFRlNG AG. Π-1 Rarün 155. Pnstfarh

SCHERING AG

Commercial legal protection implement 11 l T-N J-CO-MH-NH Ia or in a known manner with suitable inorganic bases, such as oxides, hydroxides or carbonates of the allcali or alkaline earth metals or preferably alcoholates, if appropriate in organic solvents, in a known manner

Way to 1,2,3-thiadiazole-5-carboxylic acid of the formula IY

N-.CH

Ni COOH IV

saponify, which in turn sap with common halogenating agents, such as thionyl chloride and phosphorus pentachloride, to give 1,2,3-thiadiazole-5-carboxylic acid halide of the general formula

N-CH

II

N J-CO-X VIII

! can be implemented by known methods.

Here, and X have the meaning given above and I represents an alkoxy radical, preferably a C ^ -C ^ alkoxy radical, an amino group or an alkylamino group, preferably a C ^ -C ^ alkylamino group.

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vy Ï ffi H ® LI »'* ί« r i. n. u —.l ï η · ΛνD> .. hii. U>, n · - Inrnan Usmann D ^ elflncrhrift * 5ΛΗΡΡΙΜ (5 Αβ. Π-1 PpHiR ES · Pnsffsch ES 03 11

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Intellectual Property

The process according to the invention therefore uses easily accessible starting materials and enables the desired process products to be produced in a technically simple and harmless manner,

It is of great technical advantage that the 1,2,3-thiadiazole-5-carboxylic acid azide of the formula II is not to be isolated from the reaction mixtures of its preparation, but in a one-pot process using these mixtures directly with an amine of the general formula III can be implemented.

It is particularly surprising that this procedure gives the desired process product and does not, as was to be expected, substitute the azide residue with the amine to give 1,2,3-thiadiazole-5-carboxamide.

The process according to the invention can be carried out, for example, by mixing the crude solution of the azide with the equimolar solution.

Allow the amount of the amine to drip into an inert solvent at the reflux temperature or by adding the azide solution to the amine diluted with solvent at the reflux temperature of the mixture.

The reflux intensity offers a means of control. . - 11 - CM * en m v c Board: Dr. Herbert AsmisDr. Christian BruhnHans-Jürgen Hamann Postal address: SCHERING AGD-1 Berlin 65Postbox 65031t

. U. SCHERING AG

Commercial legal protection for · the spontaneous course of the reaction.

The azide Rann can also be heated in a mixture with the amine in the presence of an inert solvent.

The temperatures are expediently 20 ° to 10 ° C., preferably 50 ° to 120 ° C. The -t is most advantageous

However, the reaction was carried out at the boiling point of the reaction mixture.

The following may be mentioned as solvents which are inert to the reactants: aliphatic and aromatic hydrocarbons such as cyclohexane, heptane, ligroin, benzene, chlorobenzene, toluene and xylene, ethers such as dioxane, tetrahydrofuran, diisopropyl ether, esters such as ethyl acetate and malonic esters, ketones such as acetone, methyl isobutyllcyl Isophorone and cyclohesanone, halogenated hydrocarbons such as ethylene chloride, chloroform and carbon tetrachloride, carbonitriles such as acetonitrile.

After the reaction has taken place, the reaction mixture is worked up in a manner known per se, for example by ablating the solvent used under normal or reduced pressure, by precipitating with water or, in 1 ', by simply filtering off the desired reaction products. In this way 1,2,3-thiadiazol-y 5-yl-ureas are obtained in an outstandingly pure form and in almost

L

! ~

Board: Dr. Herbert AsmisDr. Christian BruhnHans-Jürgen Hamann Postal address: SCHERING AG - D-1 Berlin 65Postbox 65 0311

. 12. SCHERING AG

Commercial legal protection quantitative yields and does not require subsequent cleaning operations for further use. Separation problems, such as those encountered in the reaction of 5-amino-l, 2,3-thiadiazole with isocyanates in the form of the syiretris ureas obtained as by-products, are advantageously eliminated in this case.

The following examples illustrate the implementation of the method according to the invention.

- 13 - ✓ /

^ N

ci CT} 03 T— £ Board: Dr. Herbert AsmisDr. Christian BruhnHans-Jürgen Hamann Postal address: SCHERING AGD-1 Berlin 65Pox 65 0311

. 13. SCHERING AG

Commercial legal protection i t I Example 1! 'i

Preparation of l-phenyl-3- (1,2,3-thiadiazol-5-yl) urea from 1,2,3 “thiadiazol-5-carboxylic acid ~ echlorid

A solution of 9.1 S is placed in a triple-tubed 250 ml round bottom flask with stirrer and thermometer

(0.14 mol) sodium azide in 40 ml water with kO ml j

Toluene added. For this purpose, a solution of 14.8 g (0.1 mol) 1,2,3 “is added within 15 minutes at 15 to 20 ° C! Thiadiazole-5-carb.onic acid chloride dropped in 30 ml of toluene with vigorous stirring. Then the mixture is stirred for 1.5 hours at 15-20 ° C., the toluene phase is separated off and! i dry it over magnesium sulfate. The dried 1,2,3-thiadiazole-5-carboxylic acid azide solution is mixed with 9 ml ^ ml (0.1 mol) aniline at room temperature.

Meanwhile, in a triple-tubed 250 ml I round-bottom flask with stirrer, thermometer and reflux condenser to; 80 ml of toluene preheated to 110 ° C. For this the Car- | * Acid / aniline solution within 10 minutes so yes

added dropwise that the internal temperature at 100 - 110 C

is held. With strong gas evolution, pale yellow-colored crystals are deposited immediately. The mixture is then "stirred under reflux for a further 5 minutes, cooled to 5 ° C / - i4 -

CI

O"

CO

«Fr f»

Board of Directors: Df. Herbert Asmis - Dr. Christian Bruhn Hans-Jürgen Hamann Postal address: SCHERING AG - D-1 Berlin 65Postbox ES 0311

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Commercial legal protection and filter the crystals, which are trocïuiet in Valcuum at IIO ° C to constant weight.

Yield: 19.5 S = 30.6 / 5 of theory mp: 217 ° C (decomposition) DC: eluent = ethyl acetate R ^ value: 0.25 - 15 - k- ~ \ s eji o>

(O

tl Vörstand: Dr. Herbert Asmis · Dr. Christian BruhnHans-Jüraen Hamann Postal address: SCHPR1NG AG - D-l Berlin 65Pox 65 0311

_ _ SCHERING AG

~ ^ Intellectual Property

Example 2

Preparation of l-fhenyl-3- (1,2,3-thiadiazol-5-yl) - urine off from 1,2,3-thiadiazol-5-carboxylic acid hydrazide Xn in a triple-tabulated 500 ml round-bottomed flask with thermometer and stirrer become 14.4 g (0.1 mol) 1,2,3-thiadiazole-5-carboxylic acid hydrazide dissolved in 100 ml water and 12 ml concentrated hydrochloric acid; this solution is then mixed with 200 ml of toluene. A solution of 7-25 g (0.105 mol) of sodium nitrite in 20 ml of water is added dropwise to this mixture at 0 to 5 ° C. in the course of 30 minutes. The mixture is stirred at 0 to 5 ° C. for 15 minutes and the toluene phase is separated off and dries it over magnesium sulfate. The dried 1,2,3-th.iadiazole-5-carboxylic acid azide solution is mixed with 9 »! ^ ^ 1 (0.1 mol) aniline at room temperature.

50 ml of toluene are now preheated to 110 ° C in a triple-tubed 500 ml round-bottom flask with stirrer, thermometer and reflux condenser. The dried carboxylic acid / aniline solution is added for this purpose within 10 minutes. drips that the internal temperature is kept at 100 ° to 110 ° C. Yellowish-colored crystals are deposited immediately with strong gas evolution. The mixture is then stirred under reflux for a further 5 minutes, then cooled to 5 ° C. and the crystals are filtered off with suction, which is vacuumed at 4 ° C. until the mixture is / - 16 - * \ ___ r eji σι

CO

Board: Dr. Herbert Asmis - Dr. Christian BruhnHans-Jürgen Hamann Postal address: SCHERING AGD-1 Berlin SS * Postfach 65 0311

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Intellectual Property

Constant weight dries.

Yield: 16.2 g = 73.6% of theory, mp: 217 ° C (decomposition) TLC: eluent = ethyl acetate Rp value: 0.25

The following examples explain the preparation of the starting products.

f - 17 - cjt o uj A Board: Dr.Herbert AsmisDr. Christian BruhnHans-Jürgen Hamann Postal address: SCHERING AGD-1 Berlin 55Pox 65 0311

SCHERING AG

; Intellectual property law ί

Example 3! 1,2,3-thiaöiazole-5-carboxylic acid hydra :: xd i! In a three-tubulated 100 ml round-bottomed flask with a guide ii and a thermometer, 31.6 g (0.2 Hol) of 1,2,3-thiadiazol-p-j carboxylic acid ethyl ester, dissolved in 50 ml of ethanol, are mixed with 11.0 g (0.05 22 mol) of hydrazine hydrate were added at room temperature within 5 minutes. When the temperature slowly rises to 50 ° C, yellow urine crystals separate out. You stir a hour

Ide at room temperature and then sucks off the crystals, which are dried at 40 ° C in a vacuum to constant weight.

Yield: 27.4 · s = 95% of the theorems Mp .: 145 - 14G ° C

DC: eluent = ethyl acetate - value: 0.195

Ii n - Xu - /! I ί i li Î: eji o> ii 2! 2 [ÿ Board: Dr. Herbert AsmisDr. Christian BruhnHans-Jürgen Hamann Postal address: SCHERING AGD-1 Berlin 65Pox 65 0311

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Intellectual Property

Example 4 1,2,3-Tiiiadiagol-5-carboxylic acid chloride

In a triple-tapped 250 ml round-bottomed flask with a stirrer, cooler, thermometer and drain in the fume hood, 30.0 g (0.23 mol) of 1,2,3-thiadiazole-5-carboxylic acid in 125 ml of thionyl chloride are refluxed for 2 hours heated. The.'Clear brownish solution is evaporated at 40 ° C and 15 Torr and the residue is fractionally distilled. '

Yield: 25.0 g = 7314% of theory

Kpll: 73 - 76 ° C

* / - 19 - *

Ci o »

CO

^ r r- £ Board: Dr. Herbert AsmisDr. Christian Bruhn - Hans-Jürgen Hamann Postal address: SCHERING AGD-1 Berlin 65Pox 65 0311,

. 19 _ SCHERING AG

J Intellectual property law

Example 5 1,2,3-Thiadiazole-5-carboxylic acid ethyl ester

In a triple unbound pOO ml round-bottom flask with stirrer, thermometer, reflux condenser, drying tube and gas discharge into the fume cupboard, 50 »1 ml of thionyl chloride (0.69 Hol) are drained to -I50 C and then within 30 minutes under slightly reduced pressure at 36) 2 g (0.21 mol) of ethyl formyl acetic ester seiaicarbazon at an internal temperature of -15 ° to -10 ° C. The brown solution is stirred for a further hour at -10 ° C. and then diluted with 130 ml of chloroform. The excess thionyl chloride is carefully mixed with 130 ml of a saturated potassium hydrogen carbonate solution, the temperature being kept between -10 ° and 20 ° C. The chloroform phase is separated off, washed with 50 ml of a saturated potassium hydrogen carbonate solution, dried over magnesium sulfate and evaporated at 40 ° C. in a water jet vacuum. The residue is fractionated, distilled.

P Yield: 28.6 g = 06? 6 of theory

Kp 1; L: 95 ° - 100 ° C

DC: eluent = ethyl acetate - value: 0.600 - 20 -

A

y? 'o *

t CO

T * o Board: Dr. Herbert AsmisDr. Christian BruhnHans-Jürgen Hamann Postal address: SCHERING AG D-1 Berlin 65Postbox 650311

. ao. SCHERING AG

Intellectual Property

Example 6 1,2,3-Thiadiazole-5-carboxylic acid

In a triple-tubed 4 1 round-bottom flask with stirrer, thermometer and reflux condenser, 152 lbs (15 l mol) of potassium carbonate in 1 l water are heated to 90 ° C. and 50 g (0.5 mol) of 5-methyl-l, 2,3- thiadiazole added. A solution of 158 S • (1.0 mol) of potassium permanganate in 1.5 l of water is then added dropwise at 95-100 ° C. in the course of one hour. The mixture is then heated under reflux for a further 30 minutes until the reaction solution has completely decolorized, the manganese dioxide which has precipitated is filtered off with suction and washed with 1 l of hot water. The filtrate is then concentrated in vacuo at 50 ° C to about 1 1 and acidified at 20 ° C with 80 ml of concentrated sulfuric acid. Then it is carefully extracted 5 times with 300 ml of ethyl acetate each time. The ethyl acetate extracts are dried over magnesium sulfate and evaporated to dryness in a water jet vacuum at 40 ° C.

Yield: 21.7 lbs = 33.3% of theory mp: 106 ° C (decomposition) Λ .. - 21 - o> m ψ ·

Executive Board: Dr.Herbert AsmisDr. Christian BruhnHans-Jürgen Hamann Postal address: SCHERiNG AGD-1 Berlin 65Pox 65na 11

Claims (2)

1 N_.CH! II -Ι: N !! - C0-NK-NHo IX! ! i I in inert solvents with solutions of Allcali- 'nitrites of the general formula i HeN02 X or with alkyl nitrites of the general formula> R ^ -O-NO XI in the presence of acid to give 1,2,3-thiadiazole-5-carboxylic acid azide of the formula N-ÇH 11 IN J-CO-N II \ s / 3 j, where R "is a C Ί-C, · -alkyl radical, Me is a '' 316. 26. '' / - · 'u- 1 sr "l! Board: Dr * Herbert Asmis» Dr. Christian Rruhn. Hans-Jüroen Hamann Postal address: SGHPRING AG · D-1 Rerlin 65. Pnstfarh β5Π31Ί *' '· „f SCHERINGAG m ** r> - Commercial legal protection r is a valuable metal equivalent, preferably a sodium, potassium or lithium atom and X is a kaiogenaton, preferably a chloraton. 3. The method according to claim 1, wherein hydrogen or C ^ alkyl, R2 C ^ C ^ alkyl, C ^ -Co-cycloalkyl, methyl-C ^ -Cn-cycloallcyl, phenyl, haloplienyl, C ^ -C ^ -allcylphenyl , C ^ -C ^ alkoxyphenyl, nitrophenyl, trifluoromethylphenyl, pyridyl or pyrimidyl. 9. The method according to claim 1 for the preparation of 1-phenyl-3- (1,2,3-thiadiazol-p-yl) urea. η '>; r- r; / V: \ \ \ \ 'v · \ ._ · ._ .......,. /! * »* N o n V t— 1. Process for the preparation of 1,2,3-thiadiazol-p-yl-ureas of the general formula N-CH II ίί NC -NH-CO-N I, Iin the R hydrogen or optionally one or more times by oxygen or Alkyl interrupted by sulfur atoms, R an alkyl optionally interrupted one or more times by oxygen or sulfur atoms, an optionally hydrocarbon radical which is mono- or polysubstituted by alkyl, an optionally one or more alkyl; and / or halogen and / or alkylthio and / or alkoxy and / or trifluoromethyl and / or the aromatic hollow hydrogen .substitute substituted by the nitro group, an optionally substituted heterocyclic hydrocarbon radical containing at least one N atom or ΐ / - 22 - ci <à t cn 1 ·> 1 Vnrctanrf · Of Uarhar4 AemSa. Ra Briihn _ U «ne. li'irnAK 6ΛΙΙΕ3ΙΜ /? A Ο Λ «η..τ * _« a n..u «ar SCHERINGAG“ Intellectual Property Rights R and R9 together with the N-Atora represent the ilorpholino, pi-peridino or pyrrolidino group, characterized in that one 1,2,3-thiadiazole-5-carboxylic acid azide of the formula N-CH II II N C-CO-N, II s with an amine of the general formula / R1 Η - Ν 'III R2 dissolved in an inert organic solvent and isolating the reaction product in a manner known per se, where R ^ and R ^ have the meaning given above. 2. The method according to claim 1, characterized in that the reaction at temperatures from 20 ° to 10 ° C, preferably from 50 ° to 120 ° C, is durchgeiulirt. _ O Q _ # f Ci Oi m ΊΤ Board: Or. Herbert Asmis · Or. Christian Bruhn - Hans-Jörgen Hamann Postal address: SCHERING AG · D-1 Berlin 65 «Postfach 65 0311 i. , 3rd SCHERING AG Intellectual Property Law 3. The method according to claim 2, characterized in! that the reaction at the boiling point of the heat j! mixture is carried out. t 4. The method according to claim 1, characterized in that t equimolar tiengen of the azide of the formula II and the amine I of the general formula III are implemented; 5- The method according to claim 1, characterized in that i the reaction of the azide of the formula II with the amine of the general formula III takes place in one step. j ·! 6. The method according to claim 1, characterized in that! a 1,2,3-thiadiazole-5-carboxylic acid azide of the formula II is used, which is prepared by processes known per se and is not isolated from the reaction mixtures obtained. '; i 7. The method according to claim 6, characterized in that; 1,2,3-thiaaiazole-5-carboxylic acid azide of the formula II is prepared by a) l, 2,3-thiadiazole-5-carboxylic acid of the formula n:! fi I / ^! «Ά CH il 5! i Board of Directors: Dr. Herbert AsmisDr. Christian Bruhn Hans-Jürgen Hamann Postal address: SCHERING AG · D-1 Berlin 65 · Postfach 65 C311. 24th SCHERING AG industrial property rights N - CH II | i N -C-COOH IV with chloroaniseic acid esters of the general formula Cl - CO - ORj V in an inert solvent in the presence of acid-binding agents to the mixed anhydride of the general formula ff 'N ll-C0 -0-C0-0Ro VI "" s' 3 can react and then reacted with solutions of allcalia azides of the general formula MeN ^ VII or b) 1,2,3-tbiadiazole-5-carboxylic acid halides of the general formula N_CH N 1-CO- X VIII NS /. - - 25 - /, ^ Ci Ci «i: Board: Dr. Herbert AsmisDr. Christian Bruhn · Hans-Jürgen Hamann Postal address: SCHERING AG · D-1 Berlin 65 · Postfach 65 0311 '· - 25 - SCHERING AG Industrial property protection «ί in inert organic solvents with aqueous solutions of alkali azides of the general formula i ÎÏ3N, VII! | reacted or i: c) 1,2,3-triadiazole-5-carhonic acid hydrazide of the formula 2 Board: Dr. Herbert AsmisDr. Christian BruhnHans-Jürgen Hamann Postal address: SCHERiNG AG - D-l 8eriin 65Postbox 65 0311