DE1568977A1 - Process for the preparation of derivatives of dibenzocycloheptenes - Google Patents

Description

DR.-ING. WALTER ABITJ DR. DIETER MORF

Patent attorneys

Dr. Ex]

| Münchtn 27, Pienzenauerstraße Llefon 483225 and 486415 [legrams: Chemindus Munich

January 18, 1966

8544

MBRCK & CO., ZNO.
Rahway, New Jersey 07065, V. St. A.

Process for the preparation of derivatives of
Dib enssocy oil ohept enen

The invention relates to the process for the preparation of derivatives of dibenzocyeloheptenes and in particular to a process for the preparation of 5 ~ (3 ~ "iederffiol.-Alky! Amino"? Propyl) -5H-diben8o2a, d7oyoloh © pten _f 5 "(J-Niederhol * "Alkyl aminopropylidenJ-SH ^ diljenao ^ tdJ'eyolobeptaa uM the derivatives substituted in the nucleus"

The invention taer ^ estelleii lioh their at the core in the treatment as StiamungfverbdBstpiij?

private «ind

other

In such an application, the compounds (ale base or acid addition salt) can be administered orally or parenterally Administer in the form of aqueous solutions or suspensions or orally in the form of tablets »powders, capsules or Delayed-action pills give by the combination

the association with a pharmaceutical carrier and others pharmaceutical additives in conventional catfish · The daily dose is within the range of 5 mg up to about 250 mg, preferably divided over the day Quantities taken.

An object of the invention is to provide a new process for the preparation of 5 ~ (3-lower molar alkylaminopropyl) ~ 5H-dibenzo / Er, d7oyoloheptene _t 5- (3-ni3dermol, -alkylaminopropylidene) -5H-dibenzo ^ a, d7cycloheptene and their nucleus-substituted derivatives of 5- (3-di-lower molar-alkylaminopropyl) -5H-dl as well as ^ a, d7-'0,11-dihydrocycloheptene, 5- (3-di-lower molar alkylaminoi) ropylidene) - 5H-dibenzö / a, d7-10,11-dihydrooyolohepten or their derivatives which are substituted in the nucleus ο

It allows another target of founding, 5- (3 ~ low-mol-alkylaminopropyl) ~ 5H-dibenzo / r, d7cyolohepten, 5- (3-low ex

2 -

909824/1264

mol.-AlkylaminopropylidenJ-SH-dibenBo ^ jLtd / cyclohepten imd their derivatives substituted in the nucleus by a process which is characterized in that 5 ^ (3-'niedermol.-Aikylamin (»propyl) -5H-dibenzo _i ^ a, dy ^r - '! 0.11 "dihydrocyclohepten" 5- (3 ~ nieciermol.-Alkylaminopropyliden) = 5H-dAbenzo ^ *, d7 ~ 10,11 ~ dihydrocyclohepten and their derivatives substituted in the nucleus de-hydrogenated to the corresponding 10 To form 11-unsaturated compound and then dealkylate the obtained unsaturated compound to form the desired products.

The method according to the invention can be represented as follows will: *

909824/1264

8544

H CH ₂ CH ₂ CH ₂ N (R) ₂ (A)

CHCH ₂ CH ₂ N (R) ₂ (B)

Dehydration stage H . CH ₂ CH ₂ CH ₂ NCR) ₂

CHCH ₂ CH ₂ N (R) ₂

Bn1alkylation stage

II

In the above reaction eohena, R represents low molecular weight Alkyl.

- 609824/1214

Even if the above process is particularly suitable for the preparation of 5- (3 ~ low molar-alkylaminopropyl) -5H ~ tli- j benzo ^ a, d7cyclohepten and 5- (3-lower-mol.-Alkylamlnop:? opyliden) -5H-dibenzo / ä, d7cyolohepten is, one can do it with the same ease of making those connections use which one or both of the benzene stock " parts can be substituted, provided that dor ~ like substituents unaffected during the process stay. For example, using de »in suitably substituted starting material use the above procedure to obtain 5 ~ (3 ~ lower molar alkylaminopropyl) -5H-dibenzo / a, d7oycloheptene and 5- (3-lower molar-alkyl'-minopropylidene) -5H ~ dibenzo ^ a, d7cjcloheptene Herzusteilent which before are substituted in the core, with one or more Groups such as low molecular weight alkyl, PerfIuor-niedermol.- j alkyl, amino, low molecular weight alkylamino, di-niedermol.-

alkylamino, low molecular weight alkylsulfonylamino, sharks, Hydroxy, low molecular weight alkoxy, PerfIuor-niedermolt ^ aIk- ' oxy, carboxy, low molecular weight alkylsulfonyl, perflu <r ~

i low molecular weight alkylsulfonyl, sulfamoyl, low molecular weight.

Alkylsulfamoyl and M-lower molar alkylsulfamoyl. , If one uses auob dibenzo / a, d7 ~ 10,11-dihydrooycloheptene, wel-

909824/126 *

'ORIGINAL INSPECTED

, ·; ** ■. ■■ '■■;

above at position 5 duroh a (3-Dl-low mol. ~ alk; rlaminopropyl) - or (3 ~ di ~ lower mol. alkylamino propylide> m) -Reet are substituted according to the invention as alluvial materials can use »ee is preferred, those dibenzo ^, d7-10,11-dihydrocycloheptene insert »soft at the position duroh a (3-Di-Niederaol.- £ .lkylaminopropyl) - or (3 "D-J.-lower molar-alkylaminoprc> pylidene) -Re8t substituted are, in which the main alkyl group is methyl, ethyl or is propyl.

As shown by the above reaction enema, the first stage of the process involves the dehydration of the starting material "to form the corresponding 10,11-unsaturated" compound. Dehydration can be achieved by heating any of the raw materials in the presence of a dehydrating agent such as palladium; Activated charcoal, platinum oxide and Raney nickel at elevated temperatures of 200 to SSO ⁰ O. If desired, a solvent can be used; Suitable solvents include tetrahydronaphthalene and the dimethyl ether of dietethylene glycol.

Another method to cause dehydration is νei-turns however, a halogen-containing dehydrogenating agent. Trains-

6 - 809824/126 4

; ■ ■ ■■ '' ■■ *

ORIGINAL INSPECTED

Suitable agents of this type include N-bromosuocinimide, N-chlorosuccinimide, bromine, chlorine and sulfuryl chloride. the Dehydration can sometimes be achieved in this way without the aid of a solvent, but it is preferred to use an inert organic solvent, such as carbon tetrachloride, benzene, chloroform and methylene chloride o In addition, the reaction with the halogen-containing dehydrogenating agent is preferably carried out in the presence of a small amount of a free radical generating agent such as azo-bis-butyronitrile and one Hydrogen halide = acceptor, such as fyridine, collidine, Allyl chloride or an epoxy. If you have a halogenated ges dehydrating agent ve% v «en? et« 1st * »s possible that some 10- or 11-halo-formation is formed at the same time as the desired 10,11-unsaturated compound. TJm accordingly a maximum yield of the desired. 10,11-unsaturated product, it is preferred the reaction rate obtained with a conventional one To treat hydrogen halide-releasing agents. Preferably the elimination of hydrogen halide is achieved duroa Removal of hydrogen halide using a tertiary amine, such as triethylaiiin. The one from one of the above Process obtained dehydrated product can easily untsr

-009824 / 1.2 «*

Using conventional methods can be obtained.

In the second stage of the process, the 10.1 ^ unsaturated interconnection, which comes from the 8th stage 1 gives »dealkylated to the desired monoalkylaminopropyl- or nonoalkylaminopropyldenene berivat tu form. Dealkylation can be accomplished in a number of ways. For example, you can do the one in the first stage produced 10,11-unsaturated compound with a halothioformate implemented ”to a thiourethane intermediate to produce. This implementation is most conveniently carried out in an inert solvent such as Bensolt under reflux conditions for a few hours. The urethane intermediate so produced is then hydrolyzed to give the substituted · thiooarbanyl group of thiourethane in a To convert hydrogen atom. Sine hydrolysis in a BaslsChsn Solution under reflux conditions is suitable. Before-' In some cases, however, the hydrolysis conversion is carried out by suerst the thiourethane with an oxidizing agent oxidized - water stiff peroxide in IsSlgsaur · is suitable, if also means such as perbenoic acid, pereeslesäuret Ohroms & ure or potassium permingamate can just as well be used - and so without the oxidized bisoheny product

ORIGINAL INSi> ECTED

ν- -J 008824/12 «·

with a basic solution, such as a sodium hydroxide solution, in contact.

The dealkylation .can also be achieved by the 10,11-unsaturated di-nieiermol.-alkylamino derivative condensed with a haloformate to form the corresponding urethane intermediate and that so produced Urethane intermediate product subjected to hydrolysis to convert the substituted carbamoyl group of the urethane into a water » to convert substance atom. You implementation with the halogen formate is preferably carried out in a suitable inert solvent, such as benzene, hexane or carbon tetrachloride and preferably at elevated temperature. Sas urethane will after removing the impurities by evaporation of the Solvent obtained. The urethane intermediate produced is then subjected to hydrolysis. she Hydrolysis can be either acidic or basic Carry out conditions if the latter is also preferred. When the hydrolysis is complete, what is desired is obtained Product in conventional manner, for example by extraction with a suitable solvent and evaporation

of the solvent.

The transalkylation of the 10,11-unge- formed in step 1

9 -

909824/126 * ^0RIG 'NAL inspected

saturated compound is preferably achieved by treating this derivative with a halooyane ("cyanogen halide ") to form the corresponding cyanamide derivative and by hydrolyzing the cyanamide derivative thus produced to the corresponding secondary amine.

This special dealkylation is preferably achieved by dissolving the 10,11-unsaturated derivative in one no hydroxyl group-containing solvents such as benzene or ether and slowly adding this solution to it a solution of cyanogen halide II the same solvent with stirring, allowing the alsyl halide to escape. As soon as the reaction is complete, the basic material is removed by washing with diluted acid and isolating the cyanamide derivative by evaporating the solvent. Daa cyanamide derivative is then used in a acidic or alkaline medium »with the former preferred is, hydrolyzed to the secondary amine and then in conventional Way won.

The representation of those initial / constraints, which one. Propyl side kate possess (A) can also be achieved by hydrogenation of the corresponding compounds, which

ORIGINAL INSPECTED

■ - 10 -

909824/1264

have a propylidene side chain (B). The hydrogenation can be reached simply by mm, the propylidene compound - preferably in solution in a suitable inert organic solvent such as a low molecular weight alkenol with hydrogen under pressure and in the presence of a conventional hydrogenation catalyst:], such as palladium on activated carbon, platinum oxide, "Raney nickel and the like.

The starting products of the process according to the invention are the known aminopropylidene or aminopropyl compounds which are described at various points in the literature, for example in the British patents. 858 187 and 858 188 , ia 'og ^ -nf.l of ^ jganic , Ghamistry, Volume 27, (1962), page 230 um. & n e :: their places. The compounds are prepared, for example, from the known 5H-dibenzo ^ _s d7 ~ 10,1l-dihydro-yclohepten-5-ones, which in turn can be prepared using the process described by A, G. Gope et al in a work entitled "Cyclic polyolefins,. XV, 1-methylene" 2,3,6 "7-dibenzocycloheptatrier. ^M , published in JACS 2i" (1951) pages 1673-1678 and ar other places bwöhrioben. is or you can connect the outputs »and special

-909824/1264

ORIGINAL INSPECTED

particular those which possess Subetituenten to the Bensolringsn, prepared by the Aueführungen which fW Campbell et al in a paper entitled "Synthesis of 2-acetamido ^l ~ 2 _l 3,6,7-dlbensotropllldin and 2-Aoetamido-9, 9-dimethylfluorene ", in HeIv. Chim. Aota £ & _v (1953) ι pages 1489 to 1499 appear in Hessen.

The following examples explain the invention further without restricting them

Be i β ρ 1 e 1 1 3- (3-DiaethylamlnoproPYl) -5H-dibenso / a.d7cyolohop ^ en

One erhitst 10 g of 5 ~ (3-Dimethy: i.aminopropyl) -5H-dibenso / ä \ d7-10,11-dihydrooyolohepten with 1.5 g of palladium on activated carbon (10 £ Fd) in a slow stream of nitrogen at 23O ⁰ O 5 hours under EUoren, the catalyst is filtered off from 50 ml of Bensol and the filtrate is evaporated in order to obtain 9.6 g of a dioxy oil from 5- (3-dimethylaminopropyl) -5H- ' dibenso ^ id / oyolobepten consists · '' ^fc

However, if one follows the above procedure, an equivalent one Amount of 5- (3-dimethylaminopropylidene) -5a-dib # mto ^ f, d7-

BATH ORIGINAL

10,11-dihydrocycloheptene, instead of 5- (3-3> imethylaminopropyl) -5H- = dibenzo ^ 3a _? d7-'10,11-dihydrooyolohepten is used, an equivalent amount of 5 * - (3-dimethylamino-

B e, Ι ,, β., - ρ: le 1 2

5 r (ff-Pimetbylaminopropyl) ~ 5H ~ d Lbenzo / a _T d7cyolohc; Dten and 5- (? ~ Dimethyla minopr opyl) - ftll-J, ibenzo / ä *. d7-10 ^ broa »11/10 -

dih / d rocy cloh apten

7 g of 5 - * (3-diaiethylaminopropyl) ";) H-diberizo ^, d7-10,11-dihydroeycloheptene are dissolved in 500 ml of carbon tetrachloride, mixed with 43 g (0.24 mol) of N-bromosuccinimi, adds 0, Add 5 g of azo-bis-ttyronitrile and 24; 2- (0.2 mol) of aymmet smell a collidine and keep the mixture under reflux for 15 meows while stirring Reaction 1. After standing for a few hours at the temperature of the ice cabinet, the filtered mixture of silicon dioxide and olefin hydrobromide is filtered off, the filtrate is then concentrated in vacuo, the residue is dissolved in 300 ml of anhydrous oil, 5 times 100 ml of water free from Colljiin, dried over magnesium sulfate and evaporated to dryness to give a mixture of 5- (3 ~ dimethylaiainoprc.pyl) -5H-dabenzo / a, d7oyclohepten and

- 13 -

909824/1264 _{ßAD 0R1G1NA} t

8S44

/ Af

5- (3-dimethylaminopropyl) -5H • dibenzo / e, d7-10-bromo-10,11-dihydrocyoloheptene to surrender

If one follows the procedure of the above example and uses 5- (3-dimethylaminopropylidene} -5H-dibenzo / a \ d7-10,11-d: L ~ bydrooyclohepten in place of the 5 ~ (3-dimethylaminopropyl) derivative »one obtains a corresponding mixture of 5- (3-dimethylaminopropylidene) -5H-dibenBO ^ _t d7cyclO "hepten and 5 ~ (3-l> lmethylamine (> propylidene) -5H-dibeiizo ^, d7 ^r - '10-bromo-IO, 1i-dihydrocycloheptene.

Example 3

31.6 g of the Oemisohes obtained in Example 2 is kept in 77 ml of dimethylformamide and 77 ml of iriethylamine for 2 hours with stirring and under a nitrogen atmosphere under Rüokflucisbedingungen »so the reaction mixture then poured into a 0« miβob of 300 g of you and 400 g 25 # · 8 ^{βΓ 8ohulfuric} acid a> and extracted with benzene. The aqueous sobiobt is made alkaline by adding dilute HTaOH solution and extracted with benzene. The benzene solution is washed with water until it is neutral, dried over magnesium sulphate and. evaporates to Trookne, around 31.5 g

90982A / 12edkD original

kriatallines 5- (3 ~ Mmethylaminopropyl J-SH-dibeneo ^, d7-cyclohepten to obtain. The product can be purified via its oxalate.

If following the procedure described above, and a mixture of 5- (3 ~ dimethylamino ».opropyliden) -5H-dibenzo & ι S7 ¹ O ~ om br <dihydrocyelohepten 10,11-and (3-Dime thylaminopropyliden) 5- -5H ~ dibeneo ^ a _f d7cyclohepten is used instead of the mixture given above, a corresponding amount of 5 «(3-3> imethylaminopropylidene) -5H- is obtained

7 g of ii- (3-dimethylaminopropyl) -5H-dibeneo _ji iä »d7-cyelohepten are dissolved in 20 ml of benzene and a solution of 2.76 g of methyl ortho-thioformate in 1C ml of benzene is added over the course of about 15 minutes the mixture is stirred at room temperature, the dl solution is kept under stirring for 1 1/2 hours at operating conditions, cooled to room temperature and filtered. The Piltrat is extracted with 2.5 η HOl, washed with water, dried over magnesium sulfate and im

• 15 -

909824/1264 '- _B ad original

Evaporated in vacuo. A thick, colorless oil quickly crystallizes. The resulting 5 - ^^ (N-methyl-1-methylmeroaptoformylamino) -propyi7-5H-dibenzo / a, 57oyclohepten ^ * ^{1111 can be recrietallized with} ethanol.

If the procedure described in the above example is followed and equivalent amounts of 5- (3-binethyleminopropyldene) -5H ~ diben8o ^ a _t £ 7oyolohepten are used, the corresponding 5-ZT- (H-methyl-H-methylmeroaptoformylamino) propylidene7- is obtained. 5H-dibeneo / ä, dj-oyolohepten.

B. 5- (3-methylaminopropyl) ~ 5H-f ^ * " ¹¹ ?? p / fl ι fl / byclohapten

Add 1.2 g of 5- / J- (H-Methy1-H-methylmeroapt of ormylamino) propy ^ -5H-> dlbenBo / a »j7oyol-> heptane in 13 ml egg dough, adding after cooling to home breath 2 ml of 30 g of H ₂ 0 "and then 7 ml of ice" essi ,; See below and after stirring for approximately 30 hours at room temperature, a clear, colorless solution is obtained, which is 40 ml of 11.7 η sodium hydroxide solution and diluted with 60 ml of water. The solution is extracted with benfcil, the combined benzene solution is washed with 2.5% HCl and the combined HCl extracts are made alkaline with 11.7% sodium hydroxide solution, extracted with ether, dried

■ '... ^ 16—

90982A / 1264

156B977

over magnesium sulfate and evaporated to dryness. Ee form calibrate approximately 0.6 g of 5 ~ (3-meth / laminopropyl) «5H-dibenzO"

When following the procedure of the example above and appropriate Quantities of 5 ~ ^ ~ (N ~; 4e thy 1-H-methylmer οβριοί ormylaminoJpropylidei ^ SH ^ dibcmzo ^^ dTcyolohepten used , the corresponding amount of 5 ~ (3 * "methylaminopropylid9n)« 5H «« dibenzo / a, jl7cyclohepten is obtained.

B € is ρ 1 ι »1 5

N »carbätho: gyamino) propyl7-5H-dibeng 3-

, f ^ a »d7cyclphept en

F One IGT, a solution of 27 _P i 7% (0.1 mole) of 5 "(3-DimethylaminopropylJ-SH-diberi ^ o ^ / ^ ai cyolohepten in 100 ml of benzene for one hour" au a] solution of 32.4 g of ethyl chloroformate (0.3 mol) in 100 ml of benzene are added with stirring, the reaction mixture is kept at reflux conditions for 2 hours, then extracted with 3 100 ml of 2.5 η HOl, washed with 2 χ 5 ml of water, and kneaded over magnesium sulphate and evaporate to dryness. Approximately 29.5 g of a thick oil are obtained, which is essentially pure 5- ^ 3 ~ (H-meth; rl-H-cari? ethoxyamino) ~ propyl7-5H-aibenzo / a _f <j7oyolohepten

BATH ORIGINAL

¹ T "909824/1264

* ■ ' Λ ■ .

If nan follows the procedure of the above example and uses 5- (3-Di «ethylaininopropyliden) -5H-dibetuio / i ', d7 ^> oyolohepten instead of 5- (3-dimethylaminopropyl) -5H-dibenao / a, g7-oyolohepten, receives an appropriate amount of 5-Z ^ "(N-methyl-N-oarbäthoxyamlno) propyliden7-5H-dibenso- / ä _t d7oyolohepten.

JL. 5- ( 3-Me t hy laminopr op.yI) - fSH-diben «o / a. d7oy oloheoten

Approximately 25.0 g of 5- ^ 5 "- (N-Methy 1-H-oarbäthoxyamino) propyliden7-5H-dibenso / a, d7cyolohepten are obtained 9 hours under nitrogen in a solution of 24.2 g of potassium hydroxide and 255 ml of n-butanol under Rüokfluesbedingungen, evaporated After cooling down to tree temperature, the solvent in the Vacuum, stir the residue with 200 ml of water and 30 ml η-hexane, separates the solvents and extracts the aqueous solution with 100 ml of n-hexane, then washes the combined 8ohiohten with 2 χ 100 ml of water and again old 0.5 n-8ohm sulfuric acid. The acidic solution is then made alkaline and extracted with ether, dried over magnesium sulfate and just evaporated to dryness. Approximately 19 g are obtained • in © β sohwaoh yellow, clear, thick oil »which is essential pure 5- (3-methyltiminopropyl) -5H-dibenso ^ ", djT-oyolohepten represents

- 18-

Θ0982Α / 126BkD QRlGlNAL

If one follows the procedure of the ob: .gen examples and 5-Z ^ N-methyl-N-carbäthoxyamlno) propylideJ? -5H - dibenzo - Za »d7cy <*: Lohepten instead of the 5- ^ J- (H-Metbyl-N-oarbäthoxy ~ amino) propyl7 derivative uses, one receives the corresponding Large quantities of 5- (3 ~ methylanine propylidene) ~ 5H-dibenzo- / a \ d7oyclohepten.

Example 6 A. 5 '· /? - ( H 1 methyl-H -cyanamino) t> ropyl7-5H-dib enz o / a. d7-

«-R—. i '' ■ '''ι ii i ii ιι Ι ι ιι ιι ι i ■ ι ιι

oyolohepten

You: * add a solution of 28 g of 5- (3-Di «ethylaminopropyl) -

5H-d; .l3enzo ^ ä _n d7cyclohepter. pour in 61 ml of benzene drop by drop; Zu'einer stirring solution of 9 »8 g (0.9 mol) in 30 ul Iromoyan benzene, wherein m u'-ei dares% ^r M.rmt" ntwioktlt, stirred for 3 hours at the HigohuKg Hai.mtemperatur and filtered "

to any educated precipitation su · Remove the *

? ilti-at is precipitated together with ben · oil, with the dtr was used on a Daipfbad under reduced

Drucl: eur dryness evaporated to remove excess cyanogen bromide

and remove the solvent again. Dae redoed raw.

Cyananide derivative is dissolved in benzene and the solution is washed

old diluted hydrochloric acid; also unchanged ain to remove and then steam the Btntoll solution

- 19 -

90-9824 / 1264 bad originai.

8544 JQ

one to 25 g of 5- / J- (N-methyl-H "Oyanamino) -propyi7-5fl-dibeneo / a _t d7oyclohepten ^alB yellow oil eurückeulaeeen.

If the procedure is followed by the above examples and 5- (3-dimethylaminopropylidene) ■ 5H-dibeneo / a, d / oyolohepten instead of 5- (3-DimethylaBinopropyl) -5H-dibenBo / ä ", g7-oyclohepten begins, you get a corresponding message

oyolohepten.

B "5" (3-methyleinopropyl) -SH- dibengo / ä * "d7cyolohepte: a

About 30 g of 5 - /? - (H-Methyl-H-oyana "ino) propyl7-5H-dlben" o ^ a, d7cyolohepten Buaamaen sit 500 ml Bieeeelg, 330 ml Waeeer and 50 ml concentrated nalenic acid »16 hours - the flow conditions and in this way causes the hydrolysis and decarboxylation as well as the formation of the product. The reaction mixture is concentrated to a small volume by heating it under reduced pressure, then the solution is evaporated in 250 ml of water which contains 1 ml of concentrated acid, the aqueous solution is vasoWed with insol and made alkaline with the addition of high potassium carbonate. The free Hm released in this way is extracted in Ithtr and the ether solution is

r «0-

- 900824/1264

dried free potassium carbonate. Evaporation of the ether under reduced pressure on the steam bath leaves a residue of 5- (methylaminopropy: 0-5H-dibenzo / a, d7oyolohepten

as oil back.

If one follows the procedure of the above examples and 5-Z5 " ⁴ (N-Methy 1-N-cyanamino) ~ propyliden7-5H-dibenzo25a» d7 ~ (

cyclohepten instead of 5-27 "(N-Me thy l-H-oyanamino) propyl7- ^ H-dibenzo ^^ dJcyclohepten uses a corresponding one Amount of 5- (3-Methylatiinopropylden) -5H-dlbenzo-Zeyclohepten.

If one follows similarly the procedure of Examples 1 to 6 above and 5- (3 ■ diethylaminopropyl) -5H-dibenzo ^ _f d7 ~ 10,11-dibydrooyolohepten or 5- (3-dipropylaminopropyl) -5H-dibenzo / a, d7-10 _f 11-dihydrooyolohepten anatelle of! 5- (3-dimethylaminopropyl) -5H-dibenzo ^ Si | d7-iO _f 11-dihydrocyolohepten as shown in example 1 » _{if y} is only obtained by the process according to the invention 5- (3 -Xthylaminopropyl) »5H-dibenzo ^ T _f d ^ oyolohepten or 5- (3-propylaminopropyl) - $ H-dibeneo / ja, d / oyolohepten.

When carrying out the procedure of Examples 1 bla 6 and below:? Use of the specified starting materials

• - 21 -809824 / 1 264

one holds the products listed below.

Auaganga material

5- (3-Dimethylaminopropyl) - 1. 5- (3-Methylamino-SH ^ -methyleulfonyl-dibeneopropyl) -5H-3-methyl-

/ a »d7 ~ 10 _t 11-dlhydrooyolo- eulfonyl-dibeneo-

hepten

2. 5- (3-Dimethylaainopropylidene) - 2. 5 ~ (3-Methylaalno-SH-J-trifluoromethyl-dibeneopropylidene) -5H-3- / &, ά / - 10111-dihydrooyolotrifluoromethyl «di * hepten beneo ^ y, d / cyolo-

bepten

3 x 5- (3-Di «ethyl ainopropylidene) - 3 x 5- (3-methylamino-5H-3-methoxy-diben * o ^ T, d7-propylidene) -5H-3-10,1i ^ dihydrooyolobepten methozy-dl likewise-

/ ä ₍ d7oyolohepten

4. 5- (3 "methylaminopropyl) -4 x 5- (3-methylamino-5H-3-chloro-dibenio ^ ä", d / -propyl) -5H-3-chloro-10,11-dihydrooyolobepten diben

hepten

909824/12164

Claims (1)

Qo ^l8 January 1966 Patent claims 1. Process for the preparation of 5- (3-lower molar-alkylaminopropyl) ~ 5H-dibenzo ^ a, d7oycloheptenen »characterized by the fact that a 5- (3" * di-lower molar alkylaminopropyl) -5H-dibenzo _i / 5ä, d7'-10t 11-dihydrocycloheptene is dehydrated to form the corresponding 10,11-unsaturated compound and this compound is dealkylated to the desired product. 2. Process for the preparation of 5- (3-lower mol. ~ Alkyl ~ aminopropylidene) ~ 5H dibenzo ^, djfayoloheptenen »characterized in that: to a 5 ~ \ XH ¹ V-niedex-mol.« Alkylaminopropylidene) -5H- dibenzo ^ a, d7-10,11-dihydrocyclic- hepten is dehydrated to form the corresponding 10,11-unsaturated compound and this compound dealkylated to form the desired product. 3 · The method according to claim 1, characterized in that the dealkylation by using a halogenoyane with formation of the 5- £ 5- (N-lower molar-alkyl-N-oyanamino) propyi7 compound and then hydrolyze this compound to form the desired product. ' . '". ■ - 23« 09824/1264 4. The method according to claim 2, characterized in that the dealkylation with formation of the 5- / 3- (H-niedermol.-Alkyl-N-cyananrino) propy lid end connection caused by applying a halogenoyane and then this Compound hydrolyzed to form the desired product. 5. The method according to claim 1, characterized in that dealkylation by using a halogen « formed8 to form the corresponding urethane compound and then hydrolyze the urethane compound to form the desired product. 6. The method according to claim 2, characterized daduroh _t that the dealkylation by use of a haloformate to form the corresponding urethane compound, and then causes the urethane compound is hydrolyzed under, the formation of the erwünsohten product. 7. The method according to claim 1, characterized in that the dealkylation by using sense Halogenthioformlats forming the corresponding fhioursthan connection causes and subsequently this bond hydrolyzed to form the desired product. 8. The method according to claim 2, characterized in that the dealkylation by using a Halogenthioformiate with formation of the corresponding thiourethanes Connection creates and subsequently the connection hydrolyzed to form the desired product. 9. A process for the preparation of 5- (3-lower mol. Alkylaminopropyl) -5H-dibenzo / ä, d7cycloheptenen, characterized in that a 5- (3 ~ lower mol. «Alkylaminopropyl) -5H-dibenzo £ a _t d7- 10,11-dihydrocyoloheptene is dehydrated using a halogen-containing dehydrogenating agent and this compound is dealkylated to form the desired product. 10. A process for the preparation of 5- (3- »iedermol.-Alkylaminopropyliden) -5H-dibenzo / a, d7cycloheptenen, characterized in that a 5- (3-lower mol.-Alkylaminopropyliden) -5H-» dibenzo / ä, d / -10 _f 11-dibydrooyclohepten using a ,, halogen-containing dehydrogenation- ■ - 25 - 909824/1 264 3b means dehydrated and this compound is formed dealkylated of the desired product. 11. Process for the preparation of 5- (3-low-mol.-alkyl: iaminopropyl) -5H-diben * Q ^ ä \ d7cyoloheptenen, characterized in that one ei *. 5- (3-lower molar-alkylam: nopropyl) -5H-diben8o / a, dJ7-10,11-dihydrooyolohepten using a halogen-containing dehydrating agent dehydrated, treated the material obtained with a tertiary amine and the compound obtained to form the desired product. dealkylated 12. Process «ur production of 5- (3-lower molar-alkylaminopropylidene) -5H-dibenr o / b. , d / oyeloheptenen, characterized in that a 5- (3-niedermol.-Alkyltiminopropyliden) -5H-dibenvo ^ td7 «-10f 11-dihydrooyolohepten is dehydrated using a halogen-containing dehydrogenating agent, the material contained is treated with elnnm tertiary amine and these Compound dealkylated to give the desired product. P. 13. Process for the preparation of 5- (3-methylaminopropyl) -5H-dibenzo / a, ä7oyolobepteren, thereby gekennyeiohncit, - 26 - 809824/1264 a? reacting a 5 ~ (3-Dimethy] aminopropyl) ~ 5H-dibenzo ^ »d7 0 ^1" 11-dihydrocyclohepten dehydrated to form the corresponding 10,11-unsaturated compound, and these ent "alkyIiert to form the desired product. 14. A process for the preparation of 5- (3-methylaminopropylidene) 5H ~ dibenzo ^ ä _t d7cyclohepter.en, characterized in that, a 5- (3-DifflethyJaminopropyliden) -5H-diben «o- ^ iedT-IOjH'- dihydrocycloheptene is dehydrated to form the corresponding 10,11-unsaturated compound and this compound is dealkylated to form the desired product. 15 · The method according to claim 13 «, characterized in that that you can dealkylation by using a Cyanogen halide with formation of the 5- / J- (N-methyl-N-cyanamino) propyl7 ~ compound and then hydrolyzes this compound to form the desired product. 16. Method according to claim 14t daduroh identified, that the dealkylation can be done by applying tines - 27 - 909824/1264 Cyanogen halide under Bilduni, the 5- ^ 3- (N-methyl-N-cy <inamino) propylidene7 ~ compound causes and then hydrolyzes this compound to form (it desired products. 17. The method according to claim 1; ♦ characterized in that that the Entalkylieruig by using a halogen formate with formation of the appropriate Uretban connection causes and then the urethane connection · = dung hydrolyzed to form the orv / uncooked products 18. The method according to claim 1 ', characterized in that, 'that the Entalkylierui.g by using a Halogen formates with the corresponding Urethane connection and then the urethane connection bond hydrolyzed to form the desired product 19. The method according to claim 13, characterized in that that the Entalkylieruxg by using a Halogenthioformiate with formation of the corresponding Thiourethane compound is guaranteed and then the Compound hydrolyzed to form the desired product. ₂₈ ORIGINAL BATHROOM 90982A / 1264 20α method according to claim 14t characterized} that the dealkylation by using a Halogenthioformat with formation of the corresponding Thiourethane compound causes and then this Compound to form the desired product hydrolyzed " 21. A process for the preparation of 5- (3-methylarainopropyl) -5H-dibenzo / a »d7cyclohepten3n, characterized in that a 5- (3-dimethyl: miROpropyl) ~ 5H» fiibenzo ~ ^ _r d7-10 _e 11 -dihydrocycloheipten is dehydrated using a »halogen-containing dehydrogenating agent and this compound is dealkylated to form the desired product. 22. A process for the preparation of 5 "- (3-methylaminopropylidene) -5H-dibeneo _i / a ', d7oyolohi) ptenes, characterized in that a 5- (3-dinethylaminopropylid * n) -5H' dibenzo _i / a, d7-10,11-dihydrot! yclohepten using a halogen-containing dehydrating agent dthydrated and this compound dealkylated to form the desired product. - 29 909824/1264 8544 23 Process for the preparation of 5- (3-methylaminopropyl) -5H-dibenso / a, d7eyoloheptenes ₀ because it is known that a 5- (3-dimethylaminopropyl) -5H-dibenso- / a \ d7-10.11 -dihydrooyolohepten dehydrogenated using a halogen-containing dehydrating agent _t the material obtained is treated with a tertiary amine P and the compound obtained is dealkylated to form the desired product 24 · Process for the preparation of *> - (3-Methylamlnopropyliden) -5H-diben8o / a ₉ d7oyoloheptenen »daduroh known that one is a 5- (3-Diaiethylaminopropyliden) -5H-dibenso / a _t d7-10 ₉ 11-dlhydrocyclohepten dehydrogenated using βineβ halogen-containing dehydrogenating agents treated the material obtained with a tertiary amine and dealkylated this compound to form the desired product • 30 - 909824/126 *