NO813838L - PROCEDURE FOR THE PREPARATION OF 5- (AMINOALKYL) -11-PHENYL-5H-DIBENZO (B, E) (1,4) DIAZEPINES. - Google Patents

Description

either with strong or weak acids. Examples of strong acids are hydrochloric acid, sulfuric acid and phosphoric acid. Examples of weak acids are fumaric acid, malic acid, succinic acid, oxalic acid, cyclohexane acid and the like.

To demonstrate the antidepressant utility of the compound of formula I, the procedure described by Engle-hardt, E. L., et al., J. Med. Chem. 11(2): 325 (1968), which gives a good indication of the utility of the compounds for the treatment of human depression, used as follows: 20 mg/kg of the compound to be tested was administered to five adult female mice (ICR-DUB strain ) intraperitoneally 30 min before administration of a ptotic dose (32 mg/kg, I.P.) of tetrabenazine (as the methanesulfonate salt). Thirty minutes later, the presence or absence of complete eyelid closure (ptosis) was determined in each animal. An ED^q (mean effective dose) can be determined for each tested compound in blocking tetrabenazine-induced depression in mice according to the procedure described by Litchfield et al., J. Pharmacol. Exp. Therap. 96: 99-1 13 (1949).

The preferred dibenzodiazepine as active ingredient is the compound according to example 1, namely 5-(3-dimethylaminopropyl)-11-phenyl-5H-dibenzodiazepine.

For administration of the new compounds, the active ingredient of formula I is formulated with a suitable pharmaceutical carrier into solutions, syrups, elixirs, tablets, capsules, suppositories, powders and the like.

The compounds of formula I in which the 5-position is substituted with the .3-dimethylaminopropyl radical are prepared by cyclodehydrogenation of N-(3-dimethylaminopropyl)-o-benzamido-diphenylamines as in British patent specification 907 646 using a dehydration-condensation catalyst, e.g. . phos-forpentoxyde or oxyhalides of phosphorus, preferably the latter, in a suitable solvent, e.g. 1,1,2,2^tetrachloroethane. The reaction equation is: The present invention relates to a method for treating depression in humans with certain 5-(aminoalkyl)-11-phenyl-5H-dibenzo £b , ej |j , 4j diazepines. Some of the connections are new.

Wander, A. describes in British patent document 907 646 the production of certain of the dibenzodiazepines which are produced according to the invention, for example the compound according to example 1 in the form of a maleate salt.

Wander, A. describes in British patent document 959 994 the use of reduced forms, for example 5-(aminoalkyl)-11-phenyl-1 0 ,11-dihydro-5H-dibenzo Jb ,e] £l , 4j diazepines as para-sympathological agents , antihistamines, antispasmodics, sedatives and psychic energizers.

Greig, M.E., et al, in J. Med. Chem. 1_4, No. 2 page 153

(1971) describe anaphylactic activity of certain dibenzodiazepine homologues in mice, in particular 2-chloro-5-(dimethylaminoethyl)-11-phenyl-5H-dibenzo jb,e^ jl ,4^j diazepine.

The compounds which are useful for treating the depression according to the invention have the formula

wherein R 1 and R 2 are selected from the group consisting of hydrogen or methyl,

X is selected from the group consisting of hydrogen, chlorine, bromine or fluorine,

and pharmaceutically acceptable acid addition salts thereof.

Compounds in which R 1 and R 2 are both hydrogen or one is methyl and the other is hydrogen are novel compounds.

Pharmaceutically acceptable acid addition salts are those salts which are physiologically compatible, such as salts which form

wherein X has the previously indicated meanings.

The new compounds of formula I in which the 5-position is substituted with the 3-aminopropyl radical are prepared by cyclodehydrogenation of new N-£3-(1-phthalimido)propyl]-o-benzamido-diphenylamines (IIb) after which the phthalimido moiety is converted to amino ( NH2) with hydrazine and acid. The reaction equation is:

wherein X has the previously indicated meanings. The compounds of formula III are also new.

The new compounds of formula I in which the 5-position is substituted with 3-monomethylpropylamine are prepared by further reaction of the 3-aminopropyl compound with triethylorthoformate followed by reaction with sodium borohydride (the procedure according to Crocket&Blanton, 1974(1): 55-6 Synthesis. The reaction equation is as following:

The starting benzamido compounds II (Ila and Ilb) are prepared by a modification of the procedure according to British patent document 907 646. Ortho-nitro-diphenylamine is first reductively alkylated with a solution of 3-chloropropyldimethylamine or 3-(1-phthalimido)-1-chloropropane and then the nitro part is reduced with hydrogen over palladium on carbon to form the corresponding orthoamino compound. The amino radical in the ortho position is then reacted with benzoyl halide or a substituted benzoyl halide. The reaction equation is as follows:

Q = -N(CH 3 ) 2 or 1-phthalimido.

Production 1

N-(3-dimethylaminoprdpyI)-o-amiriodiphenylamine.

A mixture of 32.0 g (0.107 mol) N-(3-dimethylamino-propyl)-o-nitrodiphenylamine (b.p. 155°/0.4 to 174°C./0.33 mm, 100 ml 200 vol%-ig ethyl alcohol and 1.5 g of 10% palladium on carbon catalyst were shaken under a hydrogen atmosphere at room temperature for 1 hour. After approximately the theoretical amount of hydrogen had been absorbed, the catalyst was filtered off through a celite filter cake and the solvent was removed under reduced pressure. The residue was distilled under high vacuum as follows:

Thin layer chromatography using 20% methyl alcohol - 80% benzene on silica gel showed that fraction 3 was relatively pure.

Manufacturing 2

N-(3-dimethylaminopropyl)-o-benzamidodiphenylamine.

To a solution of 15.5 g (0.0575 mol) N-(3-dimethyl-aminopropyl )-o-aminodiphenylamine in 100 ml pyridine cooled to 5°C under a nitrogen atmosphere was added 17.8 g (0.063 mol) benzoyl chloride . A small amount of benzene was used to wash the rest of the benzoyl chloride in the reaction vessel. The mixture was stirred for 1 hour and the vessel was closed and placed in a refrigerator over the weekend. The solvent was then evaporated under reduced pressure. The residual oil was dissolved in 100 ml of methylene chloride and the solution was washed once with 150 ml of 3 N sodium hydroxide and then three times with 250 ml of water. The methylene chloride layer was dried over magnesium sulfate and evaporated under reduced pressure. Residual pyridine was then removed under high vacuum (0.2 mm Hg) overnight. The weight of the residual oil, with free base, was 24.9 g.

Oxalate salt

To a hot solution of 4.0 g of the free base in isopropyl alcohol was added 1.35 g (0.0107 mol) of oxalic acid dihydrate. The precipitated oxalate salt of the title compound weighed 3.5 g and melted at 162-5°C. The salt after drying at 1 hour at 97-98°C (refluxing propyl alcohol) overnight at room temperature at 0.1 mm Hg gave the following analysis: Analysis: Calculated for C26<H2>9N3°5: Ct61. 37; H, 6.31; N, 9.06

Found : C,67.42; H, 6.35; N, 9.01

Manufacturing 3

By following the procedure described in preparation 2 and

use the following compounds instead of bezoyl chloride:

2-chloro-benzoyl chloride,

3-chloro-benzoyl chloride,

2- fluorobenzoyl chloride,

3- fluorobenzoyl chloride,

2-bromo-benzoyl chloride,

3- bromo-benzoyl chloride, and

4-chloro-benzoyl chloride,

was obtained: N-(3-dimethylaminopropyl)-o-(2-chlorobenzamido)

diphenylamine,

N-(3-dimethylaminopropyl)-o-(3-chlorobenzamido)

diphenylamine,

N-(3-dimethylaminopropyl)-o-(2-fluorobenzamido)

diphenylamine,

N-(3-dimethylaminopropyl)-o-(3-fluorobenzamido)

diphenylamine,

N-(3-dimethylaminopropyl)-o-(2-bromobenzamido)

diphenylamine,

N-(3-dimethylaminopropyl)-o-(3-bromobenzamido)

diphenylamine, and

N-(3-dimethylaminopropyl)-o-(4-chlorobenzamido)diphenylamine.

Manufacturing 4

N-{3-(1-phthalimido)propylj-o-aminodiphenylamine. o-nitrodiphenylamine was reacted with sodium hydride and 3-(1-phthalimido)-1-chloropropane to N-3-(1-phthalimido)propyl-o-nitrodiphenylamine then reduced with hydrogen over palladium on carbon in ethanol to form the title compound.

Manufacturing 5

When, in the method according to preparation 2, N-3-(1-phthalimido)propyl-o-aminodiphenylamine is added with each of the following acyl chlorides in excess in the same way as described in preparation 2:

2-chloro-benzoyl chloride,

3-chloro-benzoyl chloride,

2- fluorobenzoyl chloride,

3- fluorobenzoyl chloride,

2-bromo-benzoyl chloride,

3- bromo-benzoyl chloride, and

4-chloro-benzoyl chloride,

obtained:

N-3-(1-phthalimido)propyl-o-(2-chlorobenzamido)diphenylamine,

N-3-(1-phthalimido)propyl-o-(3-chlorobenzamido)diphenylamine,

N-3-(1-phthalimido)propyl-o-(2-fluorobenzamido)diphenylamine,

N-3-(1-phthalimido)propyl-o-(3-fluorobenzamido)diphenylamine,

N-3-(1-phthalimido)propyl-o-(2-bromobenzamido)diphenylamine,

N-3-(1-phthalimido)propyl-o-(3-bromobenzamido)diphenylamine, and

N-3-(1-phthalimido)propyl-o-(4-chlorobenzamido)diphneylamine.

The following examples illustrate the invention.

Example 1

5-(3-dimethylaminopropyl)-11-phenyl-5H-dibenzo

| b , not | j , 4j diazepine, fumarate p. : lj .

A stirred mixture of 18.9 g (0.05 mol) N-(3-dimethyl-aminopropyl)-o-benzamidodiphenylamine and 32.19 g (0.2 mol) phosphorus oxychloride in 50 ml 1,1,2 ,2-Tetrachloroethane was heated to 150°C under a nitrogen atmosphere for 1.5 hours. The mixture was cooled somewhat and poured over for approx. 1000 ml of crushed ice and was then diluted with enough water to a final volume of 1000 ml. The aqueous suspension was extracted twice with methylene chloride, and the methylene chloride layer was discarded. The aqueous layer was basified with 3 N sodium hydroxide and extracted with three 250 mL portions of methylene chloride. These three methylene chloride washes were combined, dried over magnesium sulfate and evaporated under reduced pressure to give a residual oil weighing 13.8 g, free base of the title compound. The oil was dissolved in hot isopropyl alcohol and reacted with 4.5 g (0.039 mol) of fumaric acid. The fumarate salt was collected by filtration, and gave 13 g after drying, melting point 168-170°C.

Analysis: Calculated for C28H29N3°4: C/71.32; H, 6.20;

N, 8.91

Found : C,71.19; H 6.19;

N, 8.89

Example 2

By following the procedure described in the example

1 and use equal molar amounts of the following compounds instead of N-(3-dimethylamino-propyl)-o-benzamidodiphenylamine: N-(3-dimethylaminopropyl)-o-(2-chlorobenzamido) diphenylamine, N-(3-dimethylaminopropyl) -o-(3-chlorobenzamido) diphenylamine, N-(3-dimethylaminopropyl)-o-(2-fluorobenzamido) diphenylamine, N-(3-dimethylaminopropyl)-o-(3-fluorobenzamido) diphenylamine, N-(3-dimethylaminopropyl )-o-(2-bromobenzamido) diphenylamine, N-(3-dimethylaminopropyl)-o-(3-bromobenzamido) diphenylamine, and N-(3-dimethylaminopropyl)-o-(4-chlorobenzamido) diphenylamine, was obtained: 11-(2-chlorophenyl)-5-(3-dimethylaminopropyl)-5H-dibenzo jb , ej Jj , 4j diazepine, fumarate,

11-(3-chlorophenyl)-5-(3-dimethylaminopropyl)-5H-

dibenzo [b , ej [j , aJ diazepine, fumarate,

11-(2-fluorophenyl)-5-(3-dimethylaminopropyl)-5H-dibenzo[b,eJ Jj , Aj diazepine , fumarate,

11-(3-fluorophenyl)-5-(3-dimethylaminopropyl)-5H-dibenzo jb,ej jj , 4j diazepine, fumarate,

11-(2-bromophenyl)-5-(3-dimethylaminopropyl)-5H-dibenzojb,e] £l , 4j diazepine, fumarate,

11-(3-bromophenyl)-5-(3-dimethylaminopropyl)-5H-dibenzo(b,eJ £l , 4 J diazepine, fumarate, and

11-(4-chlorophenyl)-5-(3-dimethylaminopropyl)-5H-dibenzo^b,ej Jj ,4j diazepine, fumarate.

Example 3

When in the procedure according to example 1, before the addition of fumaric acid, the following compounds were used instead of N-(3-dimethylaminopropyl)-o-benzamidodiphenylamine: N-3-(1-phthalimido)propyl-o-benzamidodiphenylamine,

N-3-(1-phthalimido)propyl-o-(2-chlorobenzamido)diphenylamine,

N-3-(1-phthalimido)propyl-o-(3-chlorobenzamido)diphenylamine,

N-3-(1-phthalimido)propyl-o-(2-fluorobenzamido)diphenylamine,

N-3-(1-phthalimido)propyl-o-(3-fluorobenzamido)diphenylamine,

N-3-(1-phthalimido)propyl-o-(2-bromobenzamido)diphenylamine,

N-3-(1-phthalimido)propyl-o-(3-bromobenzamido)diphenylamine, and

N-3-(1-phthalimido)propyl-o-(4-chlorobenzamido)diphenylamine,

was obtained:

5-[3-(1-phthalimido)propylj -11-phenyl-5H-dibenzo |b , ej Jj , 4Jdiazepine,

5-[3-(1-phthalimido)propylj -11-(2-chlorophenyl)-5H dibenzo jb,ej jj , 4jdiazepine,

5- [3-(1-phthalimido)propyl]-11-(3-chlorophenyl)-5H-

dibenzojb,ej jj , 4jdiazepine,

5-(3-(1-phthalimido)propylj -11-(2-fluorophenyl)-5H-dibenzo [b,ej \\ ,4]diazepine,

5- [3-(1-phthalimido) propylj-11-(3-fluorophenyl)-5H-dibenzojb,e] jj , 4] diazepine ,

5- [3-(1-phthalimido)propyl]-11-(2-bromophenyl)-5H-dibenzo[b,eJ £i , 4] diazepine ,

5-(3-(1-phthalimido)propyl]-11-(3-bromophenyl)-5H-dibenzojb,eJ Jj , 4] diazepine ,

5-[3-(1-phthalimido)propyl]-11-(4-chlorophenyl)-5H-dibenzo [b,e] jj , 4j diazepine.

Example 4

5- (3-aminopropyl)-11-phenyl-5H-dibenzo jb , ej j \ , Aj diazepine hydrochloride.

A mixture of 0.035 mol 5-[3-(1-phthalimido)propyl 1[-11-phenyl-5H-dibenzo[b,e] (1,4j diazepine, 0.039 mol hydrazine hydrate and 175 ml 190% ethyl alcohol was boiled under reflux for 2.5 hours and allowed to stand for several hours. A solution of 10 ml of concentrated hydrochloric acid in 50 ml of water was added to the mixture, and the mixture was stirred for several hours. The mixture was filtered and the filtrate evaporated under reduced pressure The hydrochloride salt was isolated by recrystallization from a suitable solvent and dried under reduced pressure.

Example 5

By following the procedure as described in Example 4 and using equal molar amounts of the following compounds in place of 5-[ 3-(f thalimido) propylj-11-phenyl-5H-dibenzo [b , ej £l ,4j diazepine: 11 - (2-Chlorophenyl)-5-£3-(1-phthalimido)propylJ-5H-dibenzojb,e3 [i , 4jdiazepine ,

11-(3-chlorophenyl)-5-[3-(1-phthalimido)propylj-5H-dibenzo|b,eJ Jl ,4jdiazepine,

11-(2-Fluorophenyl)-5-(1-phthalimido)propylJ-5H-dibenzo ^h>, ej J\ , 4j diazepine,

11-(3-fluorophenyl)-5- [ 3-(1-phthalimido) propylJ-5H-dibenzo[b,eJ ,4j diazepine,

11-(2-bromophenyl)-5-[3-(1-phthalimido)propyl 1J-5H-dibenzo[bfej f f4jdiazepine,

11-(3-bromophenyl)-5-(3-(1-phthalimido)propyl)-5H-dibenzo jfb ,ej /? ,4_Jdiazepine, and

11-(4-Chlorophenyl)-5-[3-(1-phthalimido)propylJ-5H-dibenzo|b,eJ [i , 4\ ~diazepine,

was obtained:

5-(3-aminopropyl)-11-(2-chlorophenyl)-5H-dibenzo

[b, ej jl , A~ j diazepine hydrochloride,

5-(3-aminopropyl)-11-(3-chlorophenyl)-5H-dibenzo

jb,ej [i , 4j diazepine hydrochloride,

5-(3-aminopropyl)-11-(2-fluorophenyl)-5H-dibenzo

[b,e] [1, 4J diazepine hydrochloride,

5-(3-aminopropyl)-11-(3-fluorophenyl)-5H-dibenzo

[b,e] |j , 4] diazepine hydrochloride,

5-(3-aminopropyl)-11-(2-bromophenyl)-5H-dibenzo

[b,e] [i , 4J diazepine hydrochloride,

5-(3-aminopropyl)-11-(3-bromophenyl)-5H-dibenzo

^,ej \\ , 4jdiazepine hydrochloride,

5-(3-aminopropyl)-11-(4-chlorophenyl)-5H-dibenzo

jb,e]|T, 4] diazepine hydrochloride.

Example 6

M-methyl-ll-phenyl-5H-dibenzo jb, ej , 4ydiazepine-5-propanamine, hydrochloride.

The hydrochloride salt of 5-(3-aminopropyl)-11-phenyl-5H-dibenzo jb ,ej fj ,4J diazepine was converted to a free base by partitioning this between dilute sodium hydroxide and methylene chloride, drying and concentrating the methylene chloride layer to dryness, adding dry benzene and reconcentrate to drive off benzene. The resulting free base was dissolved in a large excess of free distilled triethyl orthoformate under reflux for several hours. The mixture was concentrated in vacuo, ethanol was added and the mixture was concentrated again. The resulting imidate was dissolved in ethanol and sodium borohydride was added with stirring at 15-20°C until thin layer chromatography indicated the absence of a significant amount of the starting material. The mixture was cooled and gradually overflowed with water, followed by extraction with ethyl acetate. The ethyl acetate layer was washed neutral and salted, filtered and evaporated. The crude free base was isolated by column chromatography and reacted with ethereal hydrogen chloride and recrystallized to give the title compound.

Example 7

By following the procedure described in Example 6 and using equal molar amounts of the following compounds instead of 5-(3-aminopropyl)-11-phenyl-5H-dibenzo£b, ej jj , 4j diazepine: 5-(3-aminopropyl- ll-(2-chlorophenyl)-5H-dibenzo (b , e] jj , 4] diazepine hydrochloride, .

5-(3-aminopropyl)-11-(3-chlorophenyl)-5H-dibenzo

|b,ej [i ,4j diazepine hydrochloride,

5-(3-aminopropyl)-11-(2-fluorophenyl)-5H-dibenzo [b,ej [i ,4] diazepine hydrochloride,

5-(3-aminopropyl)-11-(3-fluorophenyl)-5H-dibenzo

[b,ej £l ,4] diazepine hydrochloride,

5-(3-aminopropyl)-11-(2-bromophenyl)-5H-dibenzo

Jb,eJ jj , 4j diazepine hydrochloride,

5-(3-aminopropyl)-11-(3-bromophenyl)-5H-dibenzo jb, ej £l , 4j diazepine hydrochloride, and

5-(3-aminopropyl)-11-(4-chlorophenyl)-5H-dibenzo |b,ej jj ,4jdiazepine hydrochloride,

was obtained: 11-(2-chlorophenyl)-N-methyl-5H-dibenzo jb,ej [i ,4j diazepine-5-propanamine hydrochloride,

11-(3-chlorophenyl)-N-methyl-5H-dibenzo [b,ej |l , 4j diazepine-5-propanamine hydrochloride,

11-(2-fluorophenyl)-N-methyl-5H-dibenzo[b,ej [lf4J diazepine-5-propanamine hydrochloride,

11-(3-fluorophenyl)-N-methyl-5H-dibenzo jb , ej ,4j diazepine-5-propanamine hydrochloride,

11-(2-bromophenyl)-N-methyl-5H-dibenzo |[b,ej [i ,4]diazepine-5-propanamine hydrochloride,

11-(3-bromophenyl)-N-methyl-5H-dibenzo jb,ej [\ ,4j diazepine-5-propanamine hydrochloride, and

11-(4-chlorophenyl)-N-methyl-5H-dibenzojb, ej [i , <Q diazepine-5-propanamine hydrochloride.

Effective amounts of the preceding pharmacologically active compounds of formula I can be administered to humans for therapeutic purposes according to the usual routes of administration and in usual forms, such as orally in solutions, emulsions, suspensions, pills, tablets and capsules, in pharma - medically acceptable carriers, and parenterally in the form of sterile solutions.

Examples of solid carriers for oral administration are such as lactose, magnesium, stearate, terra alba, sucrose, talc, stearic acid, gelatin, agar, pectin or acacia.

Examples of liquid carriers for oral administration are vegetable oils and water.

For intramuscular administration, the carrier or excipient may carry a sterile, parenterally acceptable liquid, e.g. water or a parenterally acceptable oil, e.g. arachis oil contained in ampoules.

Although very small amounts of the active ingredients of the invention are effective in the case of light therapy or in the case of administration to patients with a relatively low body weight, unit doses are usually from five mg or more, and preferably 10, 25, 50 or 100 mg or even higher, preferably administered three or four times per day, obviously depends on the situation, the compound used and the desired result. 25 to 200 mg seems to be optimal per unit dose or usual wider ranges appear to be 10 to 500 mg per unit dose. The daily dose usually required will vary from 0.5 to 20 mg/kg/day, preferably 0.5 to 10 mg/kg. The active ingredients can be combined with other pharmacologically active agents as indicated above. It is only necessary that the active ingredient constitutes an effective amount, i.e. so that a suitable effective dose is obtained in accordance with the dosage form used. Of course, several unit dosage forms can be administered simultaneously. The exact individual dose as well as the daily doses will of course be determined according to standard medical practice by a relevant doctor or veterinarian.

The following formulations illustrate the pharmacologically active compounds according to the invention.

1. Capsules

Capsules of 10 mg and 50 mg of active ingredient per capsule was produced. Where higher amounts of active ingredient are used, a reduction in the amount of lactose can be made.

Further capsule formulations preferably contain a higher dose of active ingredient and are as follows:

In each case, the selected active ingredient is mixed with lactose, starch and magnesium stearate and the mixture is encapsulated.

2. Tablets

A typical formulation for a tablet containing 5.0 mg of active ingredient per tablet is given below. The formulation can be used for other strengths of active ingredient by adjusting the weight of dicalcium phosphate. 1, 2, 4 and 5 are mixed evenly. 3 is prepared as a 10% paste in water. The mixture is granulated with starch paste and the wet mass is passed through an 8 mesh sieve. The wet granulation is dried and sieved through a 12 mesh sieve. The dried granules are mixed with calcium stearate and pressed.

The solution is prepared, clarified by filtration, filled into ampoules, sealed and autoclaved.

Claims (3)

1. Process for preparing a compound of formula wherein X is selected from the group consisting of hydrogen, chlorine, 1 2 1 bromine or fluorine, R and R are both hydrogen, or R is hydrogen when R 2 is methyl, and pharmaceutically acceptable acid addition salts thereof, characterized by that (1) o-nitrophenylamine is reductively alkylated with a solution of 3-(1-phthalimido)-1-chloropropane to form an N-3-£1-phthalimido)propyl lj-o-nitrodifenylamine compound of formula 2) the compound prepared in step (1) is reduced to form an N-(3-(1-phthalimido)propylij-o-aminodiphenylamine of formula 3) the compound prepared in step (2) is reacted with benoyl chloride of formula under formation of. a N-N3-(phthalimido)propylj-o-benzamidodiphenylamine of formula 4) the compound prepared in step 3) is cyclodehydrogenated to form a 5-(3-phthalimidopropyl)-11-phenyl-5H-dibenzo [k' eJ /j ' 4jdiazepine of formula 5) the compound prepared in step 4) is reacted with hydrazine and an acid to form a 5-(3-aminopropyl)-1-phenyl-5H-dibenzo jb, <e> j jj ,4]diazepine of formula 12 wherein R and R are both hydrogen, and 6) the compound prepared in step 5) is optionally reacted with (a) triethyl orthoformate (b) NaBH 4 while forming a N-methyl-11-phenyl-5H-dibenzo£b, ej J\ , 4 J diazepine-5-propanamine of formula 1 2 wherein R is hydrogen and R is methyl. 2. Method according to claim 1 in the production of 5-(3-dimethylaminopropyl)-11-phenyl-5H-dibenzo Jh, eJ £l ,4jdiazepine. 3. Process according to claim 1 for the production of 5-(3-dimethylaminopropyl)-11-phenyl-5H-dibenzo jb, ej [) ,4jdiazepine, fumarate [i : ij .