DE2216837B2 - - Google Patents

Description

b) for the preparation of compounds in which R ″ denotes the groupings

-CO-CH ₁ -N

R,

R ₁

or

-CO-CH ₁ -N

means with an amine of the general Formula VI or VII

HNR ₁

R ₂ (VI)

R ₃ -N- R ₁

R ₂ (VII)

implements.

Preferred deacylating agents in process variant a) are amines. Alcoholates, inorganic Hydroxides and their basic salts. Because of their solubility in various solvents in particular amines and alcoholates, such as aminopyridines, thioureas and sodium alkoliolates, used as a deacylating agent.

The reaction is preferably carried out in a solvent such as chloroform. Methylene chloride or Benzene. The reaction takes place at room temperature. can, however, by heating be accelerated. The original product can be obtained from the reaction mixture according to known methods Methods are separated. If z. B. the reaction mixture contains the deacylating agent, is this is first removed and the residue is concentrated. The concentrate is then cooled © who treated with ether. The concentrate can also be subjected to column chromatography.

The reaction in process variant b) is preferably carried out in a solvent, Lim to control the course of the reaction and to ensure a smooth reaction. Special examples Solvents which can be used according to the invention are chloroform. Carbon tetrachloride. Methylene chloride. Benzene and alcohols. The reaction runs both at room temperature and at lower or higher temperatures. In many cases it is advisable to carry out the reaction at room temperature or with heating. The reactants can be used in equimolar amounts will. In some cases, however, higher yields are obtained if one of the reactants. z. B. the amine of the general formula VI. is used in excess.

The reaction product can also be separated off from the reaction mixture by methods known per se will. If there is unreacted amine in the reaction mixture, this is used for removal of the amine with water or an acid, e.g. B. hydrochloric acid, and then treated with an organic Solvent extracted. The extract can, as required, by chromatography on silica gel getting cleaned.

The reaction of a benzophenone hydrazone of the general formula II with a haloacetyl halide of general formula III is preferably used in an organic solvent such as chloroform. Methylene chloride, carbon tetrachloride or benzo !, performed. The reaction temperature becomes preferable kept as low as possible.

To ensure a smooth course of the reaction and to increase the yield, you can add a condensing agent such as a small amount of sodium hydroxide to the reaction mixture. Sodium indrogen carbonate or sodium carbonate. The benzophenone derivative of general formula IV can optionally be separated from the reaction mixture by methods known per se. So can e.g. B. neutralized the reaction mixture, then concentrated the organic phase and with z. B. Ether.

The cyclization of the benzophenone derivative of the general formula IV is already occurring. when the compound is allowed to stand at room temperature or at lower or higher temperatures. However, the cyclization is accelerated by heating and in the presence of an alkali such as sodium hydroxide. Preferably the cyclization is carried out in a solvent such as benzene. Chloroform. Methylene chloride and carbon tetrachloride. The cyclization product of the general formula V can be separated off from the reaction mixture by methods known per se. 7. So as can concentrate the reaction mixture under reduced pressure and the concentrate are mixed with benzene or ether to crystallize the compound of general formula V.

The i, 4,5-benzotriazocine drugs according to the invention of the general formula I have a beneficial effect on the central nervous system and are therefore valuable Drug. They can be processed into medicinal preparations in a manner known per se.

Test report
a) Analgesic effect

To study the analgesic effects of the compounds of the invention, mice become electrical irritated. The mice are divided into 6 groups of 5 animals each. The individual groups the compounds of the invention listed in Table I or amidopyrine as a comparison compound administered at doses of 100 mg / kg by the oral route. 45 and 90 minutes after administration, respectively the animals are electrically stimulated by the tail (50 V. 10 msec, 1 Hz square wave). Included the number of stimuli that is necessary is determined. until the mice start screaming. The results are in Table I as the ratio of the number of stimuli required before the tracing. to the number of Stimuli listed after the tracing.

Table I R

N C

No.

CH,

CH,
H

CH,

Tcsivcrbinitiinp

CO - CH, Br

CH,

CO CH ₁ -NH - '

C ₂ H ₅

Cl

CO CH ₂ - NH - · ■ - '·' ■ '

C: O CH, ■ - NH CH, CO - CH ₂ - Br

CO - CH, - N ^ -N -i '■ Br ^ " ^N

X
Cl

Cl

Cl

Cl
H

Cl

b) Extension of the hexobarbital sleep time

Mice are divided into groups of 5 animals each. The animals of each group will be the compounds according to the invention in doses of 100 mg / kg or diazepam in a dose of 10 mg / kg administered by the oral route. Thirty minutes after the dosing, the mice are given hexobarbital sodium injected intraperetoneally at a dose of 100 mg / kg. Then the sleep time is determined. In Table II is the ratio of the sleep time of mice to which the compounds to be examined administered at the sleep time of no compound administered control mice, specified.

Table II

Number ilcr rci / c before the Tracking to the Rc! after the removal

Minutes
2.0

1.8

2.0

1.9
1.5
2.0

Amidop \ rin (comparison). . .

"Fixed line

(general formula as in table I)

60

Test connection
No. 1 RR

CH,

Cl

Factor the

Sleep7cit-

extend

gcration

> 3.6

No. R. 7th CH, 8th CH, 9 H 10 CH ₃ 11 CH ₃ 12th CH ₃

CO-O-U-NH

CO-CH ₂ -N

H
H
H

CO-CH ₂ -N;
Br

-N

Nfmuten

2.5
2.9

2.5

2.3
2.3
-> τ,

Cl

Cl

CH ₃
Br

Cl

aklor der ^: hl.if / cit extension

2.0

4.5 2.1 3.2

3.2

Diazepam (comparison) ... 3.0

550/418

c) Suppression of the coordinationrefle.xcs

The torsion bar method according to N. W. D u η h a m u. Α .. J. Amer. Pharmac. Ass. Sei .. Vol. 4ft (1957), p. 208, applied. Male mice of the ddy strain (5 weeks old, 24 to 28 g body weight) are divided into groups of 10 animals each. The individual animals are given the Diazepam and chlorpromazine administered by the oral route. I hour or 3 hours after the The mice are administered on a stick rotating around a horizontal axis (wooden stick with a diameter of 25 mm, 10 rpm). The number of mice that died within 2 minutes fall down is determined. The results are shown in Table III.

Table IFI

Test connection

control

(No administration) No. I *)

No. 2

Ni. 3

No. 4

No. 5

No. 6

No. 7

No. 10

No. Il

No. 12

Diazepam

Chlorpromazine

·) See Tables I and Π.

Dose (mg kg I

I sid.

0 0

120

240

120

240

120

240

120

240

120

240

120

240

120

240

120

240

120

240

120

240

120

240

120

240

15th

30th

10 20

! ο 0 j 0 0 0 O 1 O 0 1 0 O 0 O O O O O 0 O 1 O 0 1 0 O 1 O 1 O 0 I. 0 O 0 O 0 O O O 0 O 0 O 0 2 - » 1 0 O 1 4th T 10 6th 0 0 3 1 7th (P

.1 slit.

These results show that mice who do not have a fixed connection Movement of their legs to ensure that they do not fall off the torsion bar. who are given diazepam or chlorpromazine in low doses. These results show that diazepam and chlorpromazine are muscle relaxants Have an effect. In contrast, mice fall to which the compounds of the invention about 10 times the amount of the comparison compounds dispose! not from the torsion bar.

d) Influence on spontaneous motility Male mice of the ddy strain (5 weeks al Weight 24 to 28 g) are divided into groups of 7 animals each. The individual groups will: the compounds to be investigated in doses of -M) mg kg and diazepam as a comparison compound

ίο administered in a dose of 5 mg, kg. The animal egg no test compound is traced to the control group. 60 minutes after the administration put the mice in the middle of a wooden box open at the top. The wooden box has the dimensions 75 χ

75 χ 30 cm and is on the ground in grid squares vot Divided into 13 cm sides. During the sub The inhibition and erection of the animals is observed. To determine what is around The number of grid squares is continuously determined

th. which a mouse passes through in 1 minute. The Ergeh n.sse are compiled in Table FV

read connection

Table IV

/ \ n /: ihl the planqiudraic run through

19th
IS
19th
19th
18th
19th
19th
20th
19th
20th
17th
18th
25th

.4 -i 0.5 .3 ± 1.0 .2 i 1.0 .4 ± 0.5 .5 ± 0.5 .4 - 0.5 1.0 1.0 0.7 0.5 0.5 1.4

.0

.2 .3 .4 .6

2.5

Control (no
Sequence)

No. 1 *) f.,

No. 2

No. 3

No. 4.

No.5.:. \\ w ;;;

No. 6

No. 7

No. 8

No. 9 _

No. 10

No. 11

No. 12

Diazepam

') See Tables I and II

"Hw" the ^{results show} that the

so Hm ™ i ^ng f ^from ^ P ™ to lice em increased

rTw ™ ^{And eme increased number} ! to righting

dTe snnn, ^8en * ^caused · ^ s shows that diazepam

SÄ ^BEWE stimulates 8 ^and ng and thus for

Sf _P nI, ^Ul ! F has ^undesirable side effects. in the

VeSind, η.? · ^Stimulate "the

diher ί Ta * ^S P ° ^{n {a} ™ movement not and are

Also suitable as sedatives.

e) Acute toxicity ErS-hnl ;? ⁵⁰ -Ύ ^ ^{ε) Is determined on mice} . The ^{results are} compiled in Table V.

Table V

5.0 5.0 4.0 5.0 5.0 5.0 4.0 4.0 4.0 5.0 5.0 4.0 4.0 4.0

Number of. AufrichlbettCi! linger

1.4 4.1

± 1

0.5 .0

Connection

Number 1*).

No. 2 .

P. LD ₅₀ (mg kg 1 000 1 500

continuation

Tesi; link

No. 3

No. 4

No. 5

No. 6

No. 7

No. 8

No. 9

No. IO

No. 11

No. 12

Diazepam

♦) See Tables I and II.

II) _1n imj; kμ 1

I 3 (X)
1 5 (X)
1,300
1,500
1,200
1,800
73,000
I 500
1000
I 000
900

summary

The above pharmacological studies show that the compounds of the invention have a greater analgesic effect than amidopyrine after 90 minutes. Your sleep-prolonging Effect is much less than that of diazepam. In addition, the administration causes of the compounds of the invention at effective doses do not interfere with coordinated movements and no undesirable influence on spontaneous mobility. For this reason the compounds of the invention can be used as scdatives. Also show the connections of the invention has lower acute toxicity than diazepam on.

The examples illustrate the invention.

example 1

4 g (0.009523 mol) of 4-bromoacetyl-8-chloro-3,4-dihydro-1-methyl-6-phenyl-1,4,5-benzotriazocin-2 (1 H) -one are dissolved in 10 ml of chloroform. A solution of 9.5 g (0.1 mol) of 2-aminopyridine in 20 ml of chloroform is added to this solution. The mixture is reacted at 60 ° C. for 30 to 40 minutes with stirring. The solvent is then distilled off under reduced pressure. 1 η hydrochloric acid is added to the residue until the pH is 4. The mixture is then extracted with chloroform. The extract is washed three times with water, dried over sodium sulfate and evaporated under reduced pressure. The concentrate is column chromatographed (silica gel: eluent: benzene-chloroform-ether in a ratio of 1: 1: 1). The eluate is evaporated under reduced pressure and ether is added to the oily concentrate. Here, 8-chloro-3.4 - dihydro - 1 - methyl - 6 - phenyl - 1.4.5 - benzotriazocin-2 (l H) -one was obtained as white crystals, melting at l45 C ^r.

C ₁₆ H ₁₄ ClN ₃ O:

Calculated ... C 64.11, H 4.71, N 14.02%:
found .... C 63.86, H 4.46. N 13.80%.

Example 2

1.5 g (0.01294 MoI) 4 - bromoacetyl - 3.4 - dihydro-1-methyl-6-phenyl-1,4,5-benzotriazocin-2 (1 H) -one are obtained according to Example 1 with 13 g (0.138 mol) 2 - aminopyridine reacted, 3,4-dihydro-1 -methyl-6-phenyl-1,4,5-benzotriazocin-2 (1 H) -one being obtained in the form of white crystals. After recrystallization from chloroform-n-hexane, crystals of F. 1 IOC are obtained.

«Γ ,,, Η ,, Ν, Ο:

Calculated ... C 72.43. H 5.70, N 15.84%: ίο found .... C 72.20, H 5.85. N 15.55%.

Example 3

5 g (0.0123 mol) 4 - bromoacetyl - 8 - chlorine - 3.4 - di-

ij hydro - 6 - phenyl - 1,4,5 - benzotriazocin - 2 (I H) - one are with 20 ml of chloroform and then with a solution of 15 g (0.16 mol) of 2-aminopyridine added in 30 ml of chloroform. The mixture is reacted at 60 ° C. for 30 minutes with stirring. Afterward the solvent is distilled off under reduced pressure. The residue is with 1 η hydrochloric acid is added until the pH is 4. The mixture is then extracted with chloroform. The extract is washed three times with water.

dried over sodium sulfate and evaporated under reduced pressure. The residue will column chromatographed (eluent: benzene-chloroform-ether in a ratio of 1: 1: 1). The eluate is evaporated under reduced pressure and the oily residue is replaced with ether, whereby 8-chloro-3,4-dihydro-6-phenyl-1.4.5-benzotriazocin-2 (1H) -one is obtained in the form of white crystals. After recrystallization from chloroform-ether-hexane Crystals with a melting point of 192 to 194 ° C are obtained.

C ₁₅ H ₁₂ ClN ₃ O:

Calculated ..
Findings ...

C 63.05. H 4.23. N 14.71%: C 63.17. H 4.07. N 14.74%.

Example 4

5 g (0.0134 moles) of 4-bromoacetyl-3,4-dihydro-6-phenyl -1,4,5 - benzotriazocin - 2 (1 H) - one are according to £

4 $ Example 3 with 15 g (0.16 mol) of 2-aminopyridine set, where 3.4 - dihydro - 6 - phenyl -1,4.5 - benzo triazocin-2 (l H) -one is obtained. The compound is recrystallized from chloroform-ether-n-hexane with white crystals from m.p. 159 to 160 ° C

be jo.

C ₁₅ H ₁₃ N ₁ O:

Calculated
found .

C 71.70. H 5.21. N 16.72%: C 71.43. H 5.11. N 16.65%.

The aforementioned connection can also be used

Use of thiourea in place of 2-amine pyridine and of ethanol in place of chloroforr be made hot by the method described above.

Example 5

1 g (0.00238 Mo 4-bromoacetyl-8-chloro-3,4-dihydro-1-methyl-6-ph < nyl -1.4.5 -benzotriazocin-2 (1 H) -one dissolved. While stirring, this solution is converted into a solution of 1 (0.0147 mol) of sodium ethylai in 50 ^ ml of ethanol carried. The mixture is 40 minutes at Raun

stirred temperature and then mixed with a small amount of chloroform. The mixture is with Washed with water, dried over sodium sulfate and under reduced pressure at low temperature evaporated. The residue is column chromatographed (eluent: benzene ether Chloroform in a ratio of 1: 1: 1). The Eluai will combined and evaporated under reduced pressure. The concentrate is mixed with ether, whereby 8-chloro-3.4-dih.ydro-1-methyl-6-phenyl -1.4.5-benzotriazocin-2 (1 H) -OIi is obtained in the form of white crystals at a temperature of 145 ° C.

Example 6

In 50 ml of chloroform, 5 g (0.0108 mol) 4 - bromoacelyl - 8 - bromo - 3.4 - dihydro - I - methyl-6 - phenyl - 1.4.5 - benzotriazocin - 2 (1 H) - one dissolved. This solution is treated with a solution of 20 g (0.212 mol) of 2-aminopyridine in 2 (XImI chloroform ver.-stzt. The mixture is reacted at 30 to 40 ° C. for 30 minutes with stirring. Then will the solvent is distilled off under reduced pressure. The residue is treated with 1N hydrochloric acid added until the pH is 4. The mixture is then extracted with chloroform. The extract is washed three times with water, dried over sodium sulfate and under reduced pressure evaporated. Ether is added to the concentrate, whereby 8 - bromine - 3.4 - dihydro - I - methyl - 6 - phenyll.4.5-benzotriazocin-2 (l H) -On is obtained in the form of white crystals. After recrystallization from ethanol, crystals with a melting point of 143 to 145 ° C appear obtain.

C ₁₁₁ H ₁₊ BrN ₃ O:

Calculated ... C 55.83. H 4.10. N 12.21%:
found .... C 55.64. H 4.00. N 11.89%.

^3S

40

Example 7

A mixture of 20 g (0.0443 mol) of 4-bromoacelyl-8-bromo-3.4-dihydro-6-phenyl-1.4.5-benzotriazocin-2 (IH) -one and 1 (XImI chloroform is mixed with a solution of 94.1 g (1.0 mol) of 2-aminopyridine in 950 ml Added chloroform. The mixture is reacted at 60 ° C. for 30 to 40 minutes with stirring. That The reaction mixture is treated as in Example 6, with 8 - bromine - 3.4 - dihydro - 6 - phenyl -1.4.5 - benzotriazocin-2 ( 1 H) -one is obtained in the form of white crystals. After recrystallization from chloroform-ether-n-hexane crystals are obtained which decompose at 208 to 209 C.

C ₁₅ H _n BrN ₁ O:

Calculated ... C 54.56. H 3.66. N 12.73%:
found .... C 54.63. H 3.60. N 12.66%.

55

Example _({

10 ml of chloroform are mixed with 1 g (0.00256 mol) of 4-bromoacetyl-8-fluoro-3.4-dihydro-6-phenyll, 4,5-benzotriazocin-2 (l H) -one offset. The solution obtained is introduced into a solution of 2.4 g (0.0256 mol) of 2-aminopyridine in 15 ml of chloroform. The mixture is reacted at 50 ° C. for 5 minutes while stirring. Then the reaction mixture evaporated under reduced pressure. The concentrate is rutin hydrochloric acid while cooling with ice added until the pH is 4. The mixture is then extracted with chloroform. The F: \ trakt is washed three times with water, dried over sodium sulfate and evaporated under reduced pressure. The oily residue is treated with n-Hxin, where X - fluorine - 3,4 - dihydro - 6 - phenyl-1.4.5-benzotriazocin-2 ( I H) -On in the form of white crystals from F. 145 to 150 C obtained wild.

The [R absorption spectrum of the compound mentioned in a KBr compact shows characteristic bands at 1670, 3040, 3180 and 34 (X) cm " ^1. The nuclear magnetic resonance spectrum (solvent: CDCI,: standard: TMS) shows characteristic signals at 3.5 and 4.1 ppm (2H) and 8.8 ppm (IH).

Example 9

A mixture of 1 g (0.00247 mol) of 4-bromacclyl-S-fluorO ^ -dihydro-1-methyl ^ vphcnyl-1.4.5-benzotriaz.ocin-2 (l H) -one and 20 ml of chloroform is in a mixture of 5 g (0.053 mol) of 2-aminopyridine and Entered 50 ml of chloroform. The mixture thus obtained is stirred for 10 minutes at 30 to 40 C implemented. The reaction mixture is then evaporated under reduced pressure. That Concentrate is mixed with n-hydrochloric acid while cooling with ice used until pH is 4. That The mixture is extracted with chloroform. The extract is washed three times with water over sodium sulfate dried and evaporated under reduced pressure. The oily residue obtained is column chromatographed (Eluent: benzene-chloroform-ether in a ratio of 1: 1: 1). The eluate wire evaporated under reduced pressure. The oily concentrate is mixed with a mixture of n-Hexar and ether treated, wherein 8-fluoro-3.4-dihydro-1-methyl-6-phenyl-1.4.5-benzotriazocin -2 (I M) -or obtained in the form of white crystals from 80 to 81 ° C will.

V "u FN, O:

Calculated .
found ..

C 67.83, H 4.98. N 10.96%
C 67.68. H 5.18. N 10.71%

Example IO

1 g (0.0021 mol) of 4-bromoacetyl-8-bromo-3.4-dihydro-1-methyl- b- phenyli.4.5-benzotriazocin-2 (l H) -one is dissolved in 20 ml of chloroform. The solution obtained is introduced into a solution of 0.9 £ (0.0132 mol) of sodium ethylate in 500 ml of ethanol, while stirring. The mixture is stirred for 40 minutes at room temperature and then treated with a small amount of chloroform. The mixture thus obtained is washed three times with water, dried over sodium sulfate and evaporated under reduced pressure at low temperature. The residue is column chromatographed (eluent: benzene, ether, chloroform in a ratio of 1: 1: 1). The eluate is combined and evaporated under reduced pressure. The residue is mixed with ether, 8-bromo-3,4-dihydro-1 -methyl C -phenyl-1,4,5-benzotriazocin-2 (1H) -one being obtained in the form of white crystals. After Umkri stallisicren from ethanol crystals with a temperature of 14: to 145 ° C are obtained.

Example 11

A suspension of 2.5 g (0.00647 mol) of 4-ßromicetyl-S ^ -dihydro-S-methyl-6-phenyl-1,4,5-benzoiriazocin-2 (l H) -one in 6 cm1 chloroform is added to a solution of 10 g (0.106 mol) of 2-aminopyridine in 50 ml of chloroform vei sets. The mixture is reacted at 60 ° C. for 30 to 40 minutes with stirring. The reaction mixture is then evaporated under reduced pressure. The residue will 1 η hydrochloric acid is added until the pH is 4. The mixture is extracted with chloroform. Of the The extract is washed three times with water, dried over sodium sulfate and reduced under reduced pressure Pressure evaporated. The concentrate is mixed with ether, whereby 3,4-dihydro-8-methyl-6-phenyl, 4,5-benzotriazocin-2 (l H) -one is kept in the form of white crystals. After recrystallization from chloroform-ether-n-hexane, crystals of F. 212 to 213 C.

Calculated ... C 72.43. H 5.70, N 15.84%:
rounded .... C 72.23. H 5.41. N 15.56%.

Example 12

1 g (0.0025 mol) of 4-bromoacetyl-3,4-dihydro-1,8-dimethyl - 6 - phenyl - 1.4.5 - benzotriazocin -2 (1H) - one and 4 g (0.0425 mol) of 2-aminopyridine are reacted according to Example 11, with 3,4-dihydro-Ϊ.8-dimethyl - 6 - phenyl - 1.4.5 - benzotriazocin - 2 (1 H) - one is obtained. After recrystallizing from In chloroform-ether-n-hexane, white crystals with a melting point of 191 to 192 ° C. are obtained.

C ₁ -H ₁₇ N ₃ O:

Calculated ... C 73.09. H 6.13. N 15.04%:
rounded .... C 72.96. H 6.11. N 14.88%.

Example 13

1 g (0.0026 mol) of 4-bromoacetyl-3.4-dihydro-8-methyl-6-phenyl-1.4.5-benzodiazocine 1 H) -one and then 0.2 g (0.0026 mol) of thiourine storr are added to 50 ml of ethanol. The mixture is reacted with stirring at 60 ° C. for 1 hour and then refluxed for 45 minutes. The solvent is distilled off under reduced pressure and 14 ml of water are added to the residue. The mixture is refluxed for a few minutes and then allowed to cool. The solution is then extracted with chloroform. The extract is washed three times with water, dried over sodium sulfate and evaporated under reduced pressure. The residue is column chromatographed (silica gel: elution medium: benzene chloroform
Ether in a ratio of 1: 1: 1). The eluate is evaporated under reduced pressure and ether is added to the residue to give white crystals. After recrystallization from chloroform - ether - η - hexane, 3.4 - dihydro-8 - methyl - 6 - phenyl -1.4.5 - benzotriazocin - 2 (1 H) - one is obtained in the form of crystals with a melting point of 212 to 213 ° C.

Example 14

Ig (0.00238 mol) 4-bromoacetyl-8-chloro-3.4-dihvdro - I - methyl - ft - pheinl - 1.4.5 - bcnzotriazocin-2 (IH) -OH 30 ml of chloroform are added. The mixture obtained is in. While cooling with ice Html of an aqueous 40% solution of methylamine registered. The mixture is stirred at room temperature for 30 minutes. Then the Solvent is distilled off under reduced pressure, and the residue is mixed with water. The resulting solution is extracted with chloroform. The extract is washed three times with water.

ίο dried over sodium sulfate and under reduced Pressure evaporated. The oily residue is treated with ether, and the mixture is in the Left to stand in the cold, S-chloro-S ^ -dihydro-4-methyiaminoacetyl-1 -methyl-6-phenyl-1,4,5-benzotriazocin-2 (1 H) -one obtained in the form of white crystals will. After recrystallization from chloroform-ether-η-hexane crystals with a melting point of 160 ° C. are obtained.

C ₁₉ H ₁ ^ ClN ₄ O ₂ :

Calculated ... C 61.54. H 5.16. N 15.11%:
rounded .... C 61.29. H 5.09. N 15.40%.

Following the procedure described in Example 14, the following compounds are prepared:

1.: s.4-Dihydro-4-methylaminoacetyl-1-methyl-6-phenyl- 1.4.5-benzotriazocin-2 (1 H) -one

The compound is obtained in the form of white crystals with a melting point of 146 to 148 ° C. After recrystallization the following analytical data are obtained from chloroform-ether-n-hexane.

_3S C ₁₄ H _2n N ₄ O ₂ :

Calculated ... C 67.84. H 5.99. N 16.66%:
found .... C 67.55. H 5.83. N 16.40%.

2. 8-Chloro-3,4-dihydro-4-methylaminoacetyl-6-phenyl-1,4.5-benzotriazocin-2 (l H) -on

The compound will resound in the form of white crystals from 191 to 192 ° C. After recrystallization the following analytical data are obtained from chloroform-ether-n-hexane.

C ₁₈ H ₁₇ CIN ₄ O ₂ :

Calculated ... C 60.59. H 4.80. N 15.70%:
found .... C 60.17. H 4.61. N 15.40%.

3. 3,4-Dihydro-4-methylaminoacetyl-6-phenyl-1.4.5-benzotriazocin-2 (1 H) -on

The compound is obtained in the form of white crystals with a temperature of 64 to 166 ° C. After recrystallization the following analytical data are obtained from chloroform-ether-n-hexane.

C ₁ ^ H _1n N ₄ O ₂ :

Calculated ... C 67.10. H 5.63. N 17.38%:
found .... C 66.87. H 5.51. N 17.00%.

4. 8-chloro-3.4-dihydro-4-dimeth \ laminoicct> l-

I-methyl-6-phenyl-1.4.5-bcnzotria7ocin-2 (IH) -one:
white crystals. F. 126 C

C ₂₁₁ H ₂₁ ClN ₄ O ,:

Calculated ... C 62.41. H 5.50. N 14.56%:
rounded .... C 62.23. H 5.45. N 14.79%.

5. 8-chloro-3,4-dih \ dro-4-dirncth> laminoacctyl-

6-phenyl-1,4,5-benzotriazocin-2 (I H) -one: white crystals, m.p. 178 ^ C

C ₁₉ H ₁₉ ClN ₄ O ₂ :

Calculated ... C 61.54, H 5.16, N 15.11%; found .... C 61.35, H 5.08, N 14.90%.

6. SA-Dihydro ^ -methyiaminoacetyl-S-methyl-

6-phenyl-l, 4,5-benzotriazocin-2 <1 H) -one:

white crystals. F. 198 to 199 C after the

Recrystallize from chloroform-ether-n-hexane

C ₁₉ H ₂₀ N ₄ O ₂ :

Calculated ... C 67.84, H 5.99, N 16.66%; found .... C 67.64, H 5.90. N 16.44%.

7. S-BromOA-dihydro ^ -methylaminoacetyl-6-phenyl-1,4,5-benzotriazonn-2 (l H) -on. F. 196 C

C _ls H ₁₇ BrN ₄ O ₂ :

Calculated ... C 53.88, H 4.27. N 13.96%: found .... C 53.69, H 4.15. N 13.60%.

8. 8-Bromo-3,4-dihydro-4-methylaminoacet) II-methyl-6-phenyl-1.4.5-benzotriazocin-2 (l H) -on.

F. 167 C

C ₁₉ H ₁₉ BrN ₄ O ₂ :

Calculated ... C 54.95. H 4.61. N 13.49%: found .... C 54.88. H 4.75. N 13.55%.

9. S-bromo -. 'M-dihydro ^ -dimethylaminoacetyl-I -methyl-6-phenyl-1.4.5-benzotriazocin-2 (1 H i-one.

F. 143 C

C ₂₀ H ₂₁ BrN ₄ O ₂ :

Calculated ... C 55.95. H 4.93. N 13.05%: found .... C 55.70. H 4.52. N 12.80%.

Example 15

Ig (0.00238 moles) 4-bromoacetyI-8-chloro-3,4-dihydro - I - methyl - 6 - phenyl - 1.4.5 - benzotriazoein-2 (1 Hl-one is added to 30 ml of chloroform. The The resulting mixture is introduced into 10 ml of diethylamine solution while cooling with ice. The received The mixture is stirred at room temperature for 30 to 40 minutes, and then the solvent is added distilled off under reduced pressure. The residue is mixed with water and then with chloroform extracted. The extract is washed three times with water, dried over sodium sulfate and taken under evaporated under reduced pressure. The oily residue is with a mixture of 6 ml of acetone and 0.5 ml of water and then 1 g of tartaric acid. After the tartaric acid has dissolved. the mixture is filtered through a glass filter. The acetone solution is reduced to half of the original Reduced in volume and then left to stand in the cold. In this case, 8-chloro-3,4-dihydro-4-diethylaminoacetyl-1-methyl-6-phen \ I-1.4.5-ben / otriazocin-2 (l ll) -on-tartrate in the form of white needles. After recrystallization from acetone water 15: 1) become white crystals with a temperature of 113 to 115 ° C obtain. In a similar way the corresponding picrate is obtained from F. 175 C.

C ₂₂ H ₂₅ CIN ₄ O ₂ · C "H, N, O- (Picrali:

Calculated ... C 52.38. H 4. H). N 15.27 ",,: found. . C 52.23. H 4.36. N 14.98%. Following the procedure described in Example 15, the following compounds are prepared:

IO S-Chlor ^ dihydro ^ -äthylaminoaceiyl- '., ■ , _u ""., I ^ i α S-hftnzotnazocin-Z I Hl-on-

corresponding picrate is 199 CC ₀ H _n ClN ₄ O ₂ C ₆ H ₃ N ₃ O ₇ (picrate):

Calculated C 50.86, H 3.94, N 15.97%: found :: C 5., 14, H 3, S7, N 16.34%.

11. ^ DiethylaminoacetylO ^ dihydro- ^ phenjl-

1 4 5-benzotriazocin-2 (1H) -one, m.p. 174 to 176 ° C

.5 after recrystallization from acetone-hexane

C ₂₁ H ₂₄ N ₄ O ₂ :

Calculated .
found ..

C 69 21. H 6.64. N! 5.37%: C 69.07. H 6.62. N 15.01%.

B e i s ρ i e

16

1 u (0.00247 moles) 4-bromoacatyl-3.4-dihydro-8 - fluoro -Ί - methyl - 6 - phenyl -1,4.5 - benzodiazocines "» (Ι Hl-on is dissolved in 50 ml of benzene. This solution is poured dropwise into 10 g of a 70 ″ while stirring wäßrieen solution of monoethylamine entered. The mixture is 30 minutes at: room temperature stirred and then evaporated under reduced pressure. The residue is with water and Benzene added. The benzene phase is separated off. washed three times with water over sodium sulfate dried and evaporated under reduced pressure. The residue is made from ether-n-hexane left to crystallize. 3.4-Dihydro-4-ethylaminoacetyl-S-fluoro-i-methyl-o-phertyl-IAS-benzotriazocin-2 (l H) -one obtained in the form of white crystals. After recrystallization from ethanol Crystals with a melting point of 135 to 136 ° C were obtained.

C ₂₀ H ₂₁ N ₄ FO ₂ :

Calculated . .
found

C 65.20. H 5.75. N 15.21%: C 65.33. H 5.83. N 15.13%.

Example 17

For 30 ml of chloroform, ", g (0.00238 mol) 4 - bromoacetyl - 8 - chloro - 3.4 - dihydro - 1 - methyl-6-phenyl-1.4.5-benzotriazocin-2 (l Hl-on entered.

jo The mixture thus obtained is while cooling with ice mixed with 10 ml of diallylamine. The mixture is stirred for 30 to 40 minutes at room temperature, and the solvent is then distilled off under reduced pressure. The residue is washed with water added, and the mixture is extracted with chloroform. The extract is made three times with water washed, dried over sodium sulfate and evaporated under reduced pressure. The concentrate a mixture of 6 ml of acetone and 0.5 ml of water and then 1 g of tartaric acid are added. After the tartaric acid has dissolved. the mixture is filtered through a glass filter. The acctonous Solution is concentrated to half of its original volume and then in the cold

ditched. Here, 8-chloro-3,4-dihydro-4-dialvlaminoaetyl-1 falls -methyl-6-phenyl-1.4.5-bcn / otria / ocin-211 H) -on-tartrate in the form of white needles from After recrystallization from acetone water

(5: 1) white crystals with a melting point of 86 ° C. are obtained. C ₂₄ H ₂₁ CIN ₄ O ₂ :

Calculated., C 66.58, H 4.89, N 12.94%; found .... C 66.50, H 5.10, N 12.70%.

C ₂₄ H ₂₅ CIN ₄ O ₂ · C ₄ H _h O _h · 2H ₂ O:

Calculated ... C 53.98, H 5.06, N 8.99%; found .... C 54.06, H 5.34, N 8.91%.

Example 18

5g (0.01188MoI) of 4-bromoacetyi-8-chloro-3,4-dihydro - 1 - methyl - 6 - phenyl -1,4,5 - benzotriazocin-2 (1 H) -one are mixed with 50 ml of chloroform. the The solution obtained is introduced into 25 g (0.268 mol) of aniline. The mixture is stirred for 12 hours reacted at room temperature. Then the solvent is under reduced pressure distilled off. 0.5N hydrochloric acid is added to the residue until the pH is about 3. The mixture is extracted with chloroform. The extract is washed three times with water over sodium sulfate dried and evaporated under reduced pressure. The concentrate is mixed with ether, where 8 - chloro - 3,4 - dihydro -1 - methyl - 4 - phenylaminoacetyl-6-phenyl-l, 4,5-benzotriazocin-2 (l H) -one is obtained in the form of white crystals. After recrystallization from chloroform-n-hexane Crystals of F. 182 C obtained.

C ₂₄ H ₂₁ ClN ₄ O ₂ :

Calculated
found .

ίο

C 66.58, H 4.89. N!; 2.94%: C 66.42, H 4.86. N 12.66%.

Following the procedure described in Example 18 the following connections are made:

12. S-chloro-S ^ -dihydro ^ -phenylaminoacetyl-6-phenyl-1,4,5-benzotriazocin-2 (l H) -on.

white crystals, m.p. 130 C.

C ₂₃ H ₁₉ ClN ₄ O ₂ :

Calculated ...
found

C 65.95. H 4.57. N 13.38%: C 66.02. H 4.39, N 13.13%.

Example 19

5 g (0.0134MoI) of 4-bromoacetyl-3,4-dihydro-6-phenyl-1,4,5-benzotriazocin-2 (l H) -one are mixed with 50 ml of chloroform. The mixture is introduced into 25 g (0.206 mol) of 2,6-xylidine with stirring. That The resulting mixture is reacted for 2 hours at 60 ° C. The solvent is then added distilled off under reduced pressure. The residue is mixed with 0.5 η-hydrochloric acid until the pH value is about 3. The mixture is extracted with chloroform. The extract is made three times with water washed, dried over sodium sulfate and evaporated under reduced pressure. The concentrate is column chromatographed (elution .nrtte !: Benzene —Either — chloroform in a ratio of 1: 1: 1). That Eluate is combined and evaporated. The residue is mixed with ether, whereby 4- (2'.6'-Dimethylpheny! Amino) -acetyi- 3.4- dihydro- 6-phenyl- 1,4,5-benzoiriazocin-2 (l H) -one is obtained in the form of white crystals. After recrystallization from chloroform-ether-n-hexane Crystals with a melting point of 225 to 226 C are obtained.

C ₂₅ H ₂₄ N ₄ O ₂ :

Calculated ... C 72.79. H 5.86. N 13.58%: found .... C 72.50, H 5.75. N 13.34%.

Following the procedure described in Example 19, the following compounds are prepared.

17. 4- (2'.6'-Dimethylphenylamino) acetyl

3.4-dihydro-1-methyl-6-phenyl-1,4.5-benzotriazocin-2 (l H) -one, white crystals. F. 161 to 162 C after recrystallization

Chloroform-ether-n-hexane

13. 8-chloro-3,4-dihydro-4- (p-methoxyphenyl) -aminoacetyl-1-methyl-6-phenyl-1,4,5-benzo-

triazocin-2 (1H) -one. F. 191C

C ₂₅ H ₂₃ ClN ₄ O ₃ :

Calculated ... C 64.86, H 5.01, N 12.10%; found .... C 64.57. H 4.90, N 12.08%.

14. 8-chloro-3,4-dihydro-4- (p-methoxyphenyl) -aminoacetyl-6-phenyl-1,4,5-benzotriazocin-

2 (1H) -OIi, m.p. 197'C

C ₂₄ H ₂₁ ClN ₄ O ₃ :

Calculated ... C 64.21, H 4.72, N 12.48%: found ... C 63.92. H 4.76. N 12.53%.

15. 8-chloro-3,4-dihydro-4- (p-methylphenyl | - aminoacetyl-l-methyl-6-phenyl-1,4.5-hen / o-

triazocin-2 (I Hl-on, F. 188 C

45

55

C ₂₅ H ₂₃ CIN ₄ O ₂ :

Calculated . . . C 67.18.
found .... C 66.86.

H 5.19. N 12.54%; H 5.06. N 12.12%.

16. 8-chloro-3,4-dihydro-4- (p-methylphenvl) -aminoaccty] -6-phenyl-1.4.5-bcnzotria / .ocin-

2 (1 Hl-on. M.p. 226 C Calculated ... C 73.22. H 6.14. N 13.14%; found .... C 73.00. H 6.09. N 12.96%.

18. 8-chloro-4- (2'.6'-diniethylphenyUmino) -acetyl-3,4-dihydro-1 -methyl-6-phenyl-

1.4.5-benzotria7ocin-2 (1 H) -one, m.p. 1.70 C

C ₂₆ H ₂₅ CIN ₄ O ₂ :

Calculated ... C 67.74. H 5.47. N 12.16%: found .... C 67.58. H 5.50, N 12.00%.

19. 8-chloro-4- (2'.5 -dimethylphenylamino) -acetyl-3.4-dihydro-l-methyl-6-phE: nyl-

1,45-benzotriazocin-2 (l H) -OIi. F. 210 C

C, _{(, H: 5} C1N _{4 O:}

Calculated . . . C 67.74. H 5.47. N 12.16%: found .... C 68.03. H 5.42. N I 2.! 2%.

20. 8-chloro-4-12'.6-diethylphcnvlamino) -

acctyl-3.4-dihydr (i-l-mctnyl-6-phcnyl-

1.4.5-bcnzolriazocin-2 (l H) -one. F. 125 C.

Calculated ... C 68.77. H 5.98. N 11.46%: found .... C 68.99. H 6.02. N 11.00%.

21. 8-Clilor-3,4-dihyilro-4- | 2 \ 5'-dimethylphenylamino) acetyl-6-phenyl-1, 4,5-benz., -

lriazocin-2 | IH) -one, F. 23! C.

C ₂₅ H ₂₃ CIN ₄ O ₂ :

Calculated ... C 67.18, H 5.19, N 12.54%; found .... C 66.83, H 5.25, N 12.59%.

22. 8-Chloro-3,4-dihydro-4- (2 ', 6'-dimethylphenylamino) acetyl-6-pheny 1-1,4,5-benzo-

triazocin-2 (IH) -one, m.p. 138 C

C ₂₅ H ₂₃ ClN ₄ O ₂ :

Calculated ... C 67.18. H 5.19, N 12.54%; found .... C 67.23, H 5.12, N 12.49%.

23. 8-chloro-3,4-dihydro-4- (2 ', 6'-diethyl-

phenylamino) acetyl-6-phenyl-1,4,5-benzo-

triazocin-2 (1 H) -one, m.p.! 86 C

Cj ₁ H ₂₇ ClN ₄ O ₂ :

Calculated ... C 68.27. H 5.73, N 11.80%: found .... C 68.36. H 5.71, Nl 1.61%.

24. 3.4-Dihydro-4- (2'.5'-dimethylphenylaminol-

acetyl-6-phenyl-1,4,5-benzotriazocin-2 (1 H) -one.

F. 253 C

C ₂₅ H ₂₄ N ₄ O ₂ :

Calculated ... C 72.79. H 5.86. N 13.58%; found .... C 73.00. H 5.86. N 13.63%.

25. 3.4-Dihydro-4- (2'.6'-diethylphenylamino) -

acetyl-6-pheny] -1.4.5-benzotria2ocin-2 (1 H) -one.

F. 20! C.

Q ₇ H ₂₀ N ₄ O ₂ :

Calculated ... C 73.61. H 6.41. N 12.72%; found .... C 73.31. H 6.34. N 12.49%.

26. 8-Bromo-3,4-dihydro-4- (2'.6'-dimethylphenylamino) acetyl-6-phenyl-1.4.5-benzo-

triazocin-2 (IH) -On. Ρ ". 144 c

C ₂₅ H ₂₃ BrN ₄ O ₂ :

Calculated ... C 61.11. H 4.72. N 11.40%: found .... C 61.05. H 4.69. N 11.48%.

27. 8-Bromo-3,4-dihydro-4- (2'.6-dimethylphenylaminol-acetyl-1 -methyl-6-phenyl, 4,5-benzotriazocin-2 (1 H) -one. F. 162 C

C ₂₆ H ₂₅ BrN ₄ O ₂ :

Calculated ... C 61.79. H 4.99. N 11.09%: found .... C 62.02. H 4.94. N 10.91%.

28. 3,4-dihydro-4- (2'.6'-dimethylphenylamino) -

acetyl-1 .8-dimethy 1-6-phenyl-1.4.5-benzo-

triazocin-2 (1 H) -one. white crystals. F. 170.5 to 171.5 C after recrystallization

Chloroform-ether-n-hexane

C ₂₇ H ₁₈ N ₄ O ₂ :

Calculated ... C 73.61. H 6.41. N 12.72%: found .... C 73.34. H 6.35. N 12.57%.

Example 20

5 g (0.01 ISS mol) of 4-bromoacctyl-8-chloro-3.4-di-Ii yd ro-I-methyl-6-phenyl-1.4.5-benzotriazocin-?. ('l H) -OIi are mixed with SOmI chloroform.

The mixture is einnetragen in 25 g (0.1% Minor o-Chloran.lm. The resulting mixture is reacted for 12 hours at Raumlemperatu- with stirring. * Nschließend the solvent is distilled off Irie _yermin-1 T ₁ pressure. The residue becomes mn

SnSaSaure added until the pH value et «a 3 BetrMe The mixture is treated with chloroform and then washed three times with water, however Sodium sulfate dried and evaporated under reduced pressure. The concentrate w.rd columnar

iomatögSphiert (elution medium: benzene ether Chloroform in a ratio of 1: 1: 1). The eluate will combined and evaporated- The residue is mn Ether added, with 4- (2'-chlorophenylamino) -acetyl-

"S-chloro-S ^ -dihydro-1-raethyl-o-phenyl-IAS-bcnzotriazocine 1 H) -one obtained in the form of white crystals • vird After recrystallization from chloroform-ether-n-hexane Crystals with a melting point of 174 to 175 ° C are obtained.

C ₁₄ H _1n CIN ₄ O ₂ :

"Calculated ... C 61.68, H 4.31. N 11.99" ,: found ... C 61.42. H 4.22. M 1.87%.

₂ <According to the procedure described in Example 20, the following compounds are made:

"" - »9 8-chloro-3 4-dihydro-4- (2'-chlorophenylaminoi-" acetvi-6-phenyl-1,4,5-benzotriazocin-2l IH) -O ₁₁ .

'' F. 215 to 216 C.

^ ₃ H ₁₈ Ci ₂ N ₄ O ₁ :

Calculated . C 60.94, H 4.00, N 12.36 ",,: found -.C 61.17. H 4.04, N 12.53%.

30 8-chloro-3,4-dihydro-4- (3'-chlorophenylaminoi- * acetyl-l-methvl-o-phenyi-lAS-benzoiriazocin-

2 (1 H) -one. F. 113'C

C ₁₄ H ^ ₀ ClN ₄ O ₂ :

Calculated ... C 61.68, H 4.31, N 11.99%: found .... C 61.99. H 4 .. "53. N 11.67» ...

31 8-chloro-3,4-dihydro-4- (3'-chlorophenylamine.> I- " acetyl-6-phenvl-1,4,5-benzotnazocin-2 (! Hi-on.

F. 193 C

C ₂₃ H _1x CI ₂ N ₄ O ₂ :

Calculated .. C 60.94, H 4.00, N 12.36%: found .... C 61.02. H 4.25. N 12.49%.

32.3,4-Dihydro-4- (3'-chlorophenylamino) -aeei \ l-

1-methyl-6-phenyl-1.4.5-benzotriazocin-2 (IH) -OIi.

F. 152 C

C ₂₄ H ₁₁ CIN ₄ O ₂ :

Calculated ... C 66.58. H 4.89. N 12.94%: found .... C, 66.43. H 4.82. N 12.94%.

33. 3,4-Dihydro-4- (2'-chlorophenylaminoi-acct \ l 8-methyl-6-phenyl-1.4.5-bcnzotriazocin-2ll Hl-one.

F. 202 C

C ₂₄ H ₂₁ ClN ₄ O ₂ :

Calculated ... C 66.58. 114.89. N 12.94%: found .... C 66.78. H 4.81. N 12.83 ",,.

34. 3.4-r> ihydro-4- (2'-chlorophenylamino) -aetyl-1 S-dimethyW-phcnyl-IA.'vbenzotria / ocm-

'211 H) -OIi. F. 181 C

C ₂₅ H ₂₁ ClN ₄ O ,:

Calculate! ...
found

C 67.IX. 115.19. N 12.54%:
C 67.01. II 5.09. N 12.11 "".

35. 8-Bromo-3,4-dihydro-4- (3'-chlorophen \ lamino) -acctyl-6-phenyl-1,4.5-benzolriazocin-2 (l Hj-on.

white crystals. F. 192 to 193 C after the
Recrystallize from chloroform ether hexane

C _2. , H _I8 BrCIN ₄ O ₂ :

Calculated ... C 55.49. 113.64. N 11.26%:
found .... C 55.29. H 3.52. N 11.03%.

36. 8-Bromo-3,4-dihydro-4- (3'-chlorophenylamiiio) -acetyl-1-met hyl-6-phcnyl-1.4.5-benzene riazodn-

2 (1 H) -OIi.'F. 127 C

C ₂₄ H ₂₀ BrClN ₄ O ₂ :

Calculated ... C 56.32. H 3.94. N 10.95%:
found .... C 56.00. H 3.92. N 10.51%.

37.3.4-E) ihydro-4- (3'-chlorophenylamino) -acetyll.8-dimethyl-6-phenyi-1.4.5-benzotriazocin-

2 (f H) -On. F. 145 to 146 C.

C ₂₅ H ₂₁ CIN ₄ O ₂ :

Calculated ... C 67.18. H 5.19. N 12.54 ° ,,:
found .... C 66.XK. H 5.12. N 12.14%.

Example 21

5 g (0.01 IKX moles) 4-1 ^ 01 ^^ 1-8 ^ 11101-3.4 ^ 11-hydro - 1 - methyl - 6 - phenyl - i .4.5 - benzotriazocin-2 (1H) -OIi 50 ml of chloroform and then 25 g (0.233 mol) of Bcn / ylainin are added. The resulting mixture is reacted with stirring for 4 hours at room temperature. Afterward the solvent is distilled off under reduced pressure. The residue is with 0.5N hydrochloric acid added until the pH is about 3. Chloroform is added to the mixture and then three times washed with water, dried over sodium sulfate and evaporated under reduced pressure. The residue is column chromatographed (solvent: benzene, ether, chloroform in the ratio 1: 1: 1). The eluate is combined and evaporated. Ether is added to the residue, 4 - (benzylamino) - acetyl - 8 - chloro - 3.4 - dihydro-I -methyl -6-phenyl-1.4.5-benzotriazoein-2 (1 H) -one is obtained in the form of white crystals with a melting point of 137 to 138 ° C.

C ₂₅ H ₂₃ ClN ₄ O ₂ :

Calculated . ..
found

C 67.18. H 5.19. N 12.54%:
C 67.12. H 5.12. N 12.16%.

Following the process described in Example 21, the following compounds are established posed:

38. 8-chloro-3,4-dihydro-4- (l -phenylethylamino) -

acetyl-l-methyl-o-phenyl-lAS-benzotriazocin-

2 (1 H) -one. F. 160 C

. <H ₁₁ ClN _-1 O-

Calculated. .
loved it. . .

C 67.1X. H 5.19. N 12.54%: C 66.97. H 5.37. N 12.14 ¹ O.

40.3.4-Dihydro-4- (bcn / ylarnino) -acctyl-6-phenyl.4.5-bcnz.otriazocin-2 ( I H) -on. white crystals.

F '. 198 to 205 C after recrystallization

Chlorofonn-n-l Icxan

('.4H ₂₂ N ₄ O ₂ ■ W ₁ 0:

Calculated ... C 69.22. H 5.81. N 13.45%: found .... C 69.67. H 5.25. N 13.32%.

41. 8-Bromo-3,4-dihydro-4- (benzylamino) -acetyl-

I-methyl-6-phenyl-1.4.5-bcnzotriazocin-2 (1 H) -one.

F. 147 C

C ₂₅ H _2-1 BrN ₄ O ₂ :

Calculated ... C 61.11. H 4.72. N 11.40%: found .... C 60.82. H 4.69. N 11.00%.

42.3,4-Dihydro-4- (benzylamino) -acetyl-

I.S-dimethyl-ö-phenyl-1.4.5-benzotriazocin-

'2 (IH) -on. F. 142 C

Bererhncl ... C 73.22. H 6.14. N 13.14%: found .... C 73.00. H 6.17. N 12.89%.

Example 22

In 30ml chloroform Ig (0.0023KMoI) 4 - Broniacetyl - 8 - chloro - 3.4 - dihydro - 1 - methyl-6-phenyl-l.4.5-benzotriazocin-2 (l H) -on entered. This mixture is in 10 ml of aqueous while cooling with ice. 40% igc solution of piperidine entered. The mixture thus obtained is stirred at room temperature for 30 minutes. Then the Solvent distilled off under reduced pressure. The residue is mixed with water. That

■ 40 mixture is extracted with chloroform. The extract is washed three times with water, dried over sodium sulfate and evaporated under reduced pressure. The oily residue is replaced with ether, and the mixture is left to stand in the cold, whereby K-chloro-3,4-dihydro-4-piperidinoacetyl-1-methyl-6-phenyl-1.4.5-benzotriazodn-2 (1 H) -or is obtained in the form of white crystals. After the recrystallization from chloroform-n-Äthei Hexar crystals are obtained, melting at 171 C.

C ₂₃ H ₂₅ ClN ₄ O ₂ :

Calculated ...
found

C 65.00. H 5.93. N 13.19%: C 64.73. H 5.84. N 12.93%.

Following the process described in Example 22, the following compounds are established posed:

43.S-chlorine ^^ - dihydro ^ -pyrrolidinoacetyl-

1-methyl-6-phenyl-1,4.5-benzotriazocin-2 (1 H) -one.

F. 154 C

C ₂₆ H ₂₅ ClN ₄ O ₂ : C. 67.74. H 5.67. N 12.16%: C ₂₂ H ₂₁ CIN ₄ O ₂ : C. 64.30. Calculated ... C. 67.45. H 5.40. N 12.42%. Calculated . .. C. 64.53. found .... found

39. 8-chloro-3,4-dihydro-4- (1-phenylethylamino) -

acetyl-6-phenyl-1.4.5-benzotriazocin-2 (l H) -one.

F. 146 C

H 5.64. N 13.64%; g H 5.59. N 13.56%.

44.S-chloro ^ M-dihydro ^ -morpholinoacetyl-

1-mcthyi-6-phenyl-1.4.5-benzotriazocin-2 (1 H) -one

F. 142 C

409 550/4

C ₂₂ H ₂₁ ClN ₄ O ,:

Calculated ... C 61.89. H 5.43. N 13.12%: found .... C 61.59. H 5.34. N 12.92%.

45.8-chloro-3.4-dihydro-4-morpholiiu) acet \ l-6-phenyi-1.4.5-benzotria / ocin-2 ( I H) -on. F. 117 C

C ₂₁ H ₂₁ ClN ₄ O.,:

Calculated . . .
Found

C 61.09. H 5.13. N 13.57%: C 80.80. II 4.97. N 13.22%.

46.S-chloro-S ^ -dihydro ^ -piperidinoacetyl-6-phenyl-1,4,5-benzotriazocin-2 (l H) -On, F. 129 C

C ₂₂ H ₂₃ CIN ₄ O ₂ :

Calculated ... C 64.30. H 5.64. N 13.64%: found .... C 64.40. H 5.67, N 13.48%.

47.S-Chlor ^^ - dihydro ^ -pyrrolidinoacctyl-6-phcnyl-1,45-benzotriazocin-2 (l H) -on. F. I6S C

C ₂₁ H ₂₁ ClN ₄ O ₂ :

Calculated ... C 63.55. H 5.33. N 14.12%: found .... C 63.24. H 5.19. N 13.77%.

48.3,4-Dihydro-4-pyrrolidinoacetyl-6-phenyl-4,5-benzotriazocin-2 (I. H) -on. T-. 103 C

C ₂₁ H ₂₂ N ₄ O ₂ :

Calculated
found .

C 69.59. H 6.12. N 15.46%; C 69.98. H 6.43. N 15.10%.

49. <S-Bromo-3,4-dihydro-4-piperidinoacetyl-6-phenyl-1,4.5-benzotriazocin-2 (l H) -on. F. 130 C.

C ₂₂ H ₂₁ BrN ₄ O ₂ :

Calculated ...
found ....

C 58.03. H 5.09. N 12.30%: C 58.15. H 5.01. N 12.25%.

50.S-bromo ^ -dihydro ^ -piperidinoacetyl-

1-methyl-6-phenyl-1.4.5-benzotriazocin-2 (1 H) -one

F.133 C

C ₂₃ H ₂₅ BrN ₄ O ₂ :

Calculated ... C 58.85. H 5.37. N 11.94% found C 58.50. H 5.24. N 11.50%.

Example 23

In 30 ml of chloroform (0.00238 mol) 4-bromoacetyl-8-chloro-3.4-dihydro-1-methyl-6-phenyl-1.4.5-benzotriazocin-2 (1 H) -one is dissolved. The solution obtained is added dropwise to a solution of 5 g (0.058 mol) of piperazine in 60 ml of chloroform. After the addition is complete, the mixture is stirred for 30 minutes at room temperature. After the addition of water, the reaction mixture is washed 5 times with water. The chloroform phase is separated off, dried over sodium sulfate and evaporated under reduced pressure. Ether-n-hexane is added to the residue, whereby 8 - chloro - 3.4 - dihydro - 1 - methyl - 4 - _p ip _Cr . '

azinoacetyl-6-phenyl-I.4.5-benzotriazocin-2 (i H) -one is obtained as a white powder.

The IR absorption spectrum of this compound in a KBr compact shows characteristic bands at 1675 cm " ¹ and 3400 cm "'. The nuclear magnetic resonance spectrum (solvent: CDCl _3. Standard · TMS) shows characteristic sienals at 19 nm (1 H). 2.68 ppm (4H). 2.87 ppm (4H). 3.3 ppm (3H _1. / N

3.8 ppm (2H). 4.06 ppm (IH). 5.23 ppm (I H) and 7.1 up to 7.6 ppm (HH).

According to the Ver the following connections are made:

51. 8-biom-3,4-dihydro-1-melhyl-4-pipera / ino-

acetyl-6-phenyl-1.4.5-bcii7otriazocin-2 (l H) -one.

F. 143 to 145 C.

ίο C ₂₂ H ₂₄ BrN ₅ O ₂ :

Calculated ... C 56.18. H 5.14. N 14.89%;
found .... C 56.23. H 5.22. N 14.75%.

52. S-fluoro-.M-dihydro-l-methyl ^ -piperazino-

acetyl-6-phenyl-1.4.5-benzotriazocin-2 (l H) -one.

F. 64 to 66 C.

The IR absorption spectrum of this compound in a KBr compact shows characteristic bands at 1670, 1700 and 3300 cm '. The nuclear magnetic resonance spectrum (solvent: CDCl _3. Standard • MS) shows characteristic signals at 2.23 ppm -, "λ ^{J1 ppm (4H>} < ² · ⁹⁰ HP '" HH), 3.33 ppm (3H), 3.82 ppm (2H). 4.08 ppm (IH), 5.24 ppm (IH) and 6.7 to 7.8 ppm (8H).

Example 24
In 200ml chloroform 5 g (0.01188MoI]

⁴ -Bromoacetyl-8-chloro-3,4-dihydro-r-methyl-6-phenyl-1.4 5-benzotriazocin-2 (1H) -one dissolved. The crhalnm, nx ^{Ung is introduced into a} solution of 1.67 g UMH19 Mo!) Hexamethylenetetramine in chloroform. The mixture will last 20 to 30 minutes

nei temperature hardly stirred, and then weracn / ₅ of the initial Lösungsrnittelvolumens distilled off under reduced pressure. The residue is mixed with ether, whereby (8-chloro-3.4-din.uro - I - methyl - 2 - oxo - 6 - phenyl - 1.4.5 benzotri-

azocin - 4 - y |). carbonylmethylhexamethylenetetraminum monobromide obtained in the form of white crystals. which decompose at 180 to 185 C.

C ₂₄ H ₂₇ BrCIN ₇ O ₂ :

Calculated ... _C 51.39. H 4.85. N 17.48%:
found ... . _C 51.05. H 4.99. N 17.18%.

8 IhZ ^L

wfrH

Example 25

^From 'S <° · ΟΟ238 mol) 4-bromoacetyl-''- ^met "yl-6-phenyl-1.4.5-benzo ^{m 15 ml of} chloroform is introduced into ^{5 g y dra} ^ n. ^{Stir for} 15 hours at room temperature. · ^Anschli is eating eineedampft the reaction under reduced pressure. ^entral -Salzsäure ^is treated ^with 1 "to m ^{Wa 3 beträ} ^ · ^the mixture is then added ⁰ ^ ^chlorine oform. The chloro- ³ " ^{to 5 times} washed with water, ^f i" ^e '"" ei under reduced

^e ! ^{ng mpft} - ^{the got sim} ? ^becomes ChloÄ ^ ^a l ° ⁸ / ^a P "-ert (eluent: benzene

i " ^{here in the} ratio 1: 1: i). The eluate

^{Dk D}

dernH
wed 50

em

8-ChInr ι
acetyl ί:

^gp H offset, where

ocin-2 (1H) -one in

/ tf

Form pale yellowish crystals is obtained, the decompose at HK) C.

C ₂₄ H ₂₂ N ₅ CIO ₂ :

Calculated ... C 64.35, H 4.95. N 15.64%:
found .... C 64.43, H 5.16. N 15.34%.

Example 26

1 10 g (0.04070 mol) of 2-amino-5-chlorobenzophenone hydrazone are dissolved in 5 (K) ml of chloroform. This | _O solution is added under cooling with ice and with stirring, with 30 ml of O, 5N sodium hydroxide solution. 30 g (0.1486 mol) of bromoacetyl bromide are added dropwise to this mixture at 0 to 5 ° C. After the addition is complete, the mixture is stirred for 30 minutes. The acidic solution obtained is neutralized with 0.5N sodium hydroxide solution. The chloroform phase is then separated off , washed three times with water, dried over sodium sulfate and evaporated under reduced pressure. The concentrate obtained is mixed with ether, whereby 18.8 g of 2-bromoacctamido-5-chlorobenzophenone bromoacetylhydrazone are obtained in the form of white crystals. The yield is 94.8% Recrystallization from chloroform-ether-hexane gives crystals with a melting point of 161 ° C.

C ₁ -H ₁₄ ClBr ₂ N ₃ O ₂ :

Calculated ... C 41.88, H 2.89. N 8.62%:
found .... C 42.03, H 2.80. N 8.44%.

2. 10 g (0.02051 moles) of the above prepared 2 - bromoacetamido - 5 - chlorobenzophenone bromoacetylhydrazone are dissolved in 1 l of chloroform. The solution is cooled to 10 to 15 C and then a solution of 1.5 g (0.0375 mol) of sodium hydroxide in 200 ml of water is added while stirring. That The mixture is kept at 10 to 15 C for 1 to 1.5 hours. The temperature is then increased to 25 to 33 C, and the mixture is held at this temperature for 5 to 6 hours. After full Reaction, the chloroform phase is separated off. Washed 3 times with water over sodium sulfate dried and evaporated under reduced pressure. The concentrate is mixed with ether, whereby 4-bromoacetyl-8-chloro-3,4-dihydro-6-phenyli.4.5-benzotriazocin-2 (1 H} -one is obtained in the form of white crystals. After recrystallizing from Chloroform-n-hexane crystals with a melting point of 211 to 212 ° C. are obtained.

C ₁₇ H ₁₃ ClBrN ₃ O ₂ :

Calculated ... C 50.21, H 3.22. N 10.33%:
found .... C 50.49, H 3.30. N 10.03%.

Example 27

I. 20 g (0.09466 mol) of 2-aminobenzophenone hydrazone and 100 g (0.4953 mol) of bromoacetyl bromide implemented according to Example 26, wherein 30 g (0.662 mol) of 2-bromoacetamidobenzophenine bromoacetylhydrazone can be obtained in 70% yield After recrystallization from Chlorofoim-Äthern-Hexane white crystals of 151 ° C. are obtained.

C ₁₇ H ₁₅ Br ₂ N ₃ O ₂ :

Calculated ... C 45.06, H 3.34, N 9.27%;
found .... C 44.79, H 3.10. N 8.94%.

55

2. IUg (<M) 22I mol) of that prepared above 2- Bromaeelamidobenzophcnonbromacetylhydrazons are mixed with a solution of 1.5 g (0.0375 mol) Sodium hydroxide reacted in 200 ml of water according to Example 26, 4-Bromaeetyl-3.4-dihydro-6-phenyl-1.4.5 - benzotriazocin - 2 (1 H) -one is obtained. After recrystallization from chloroform-ether-n-hexane white crystals of 190 ° C. are preserved.

C ₁₇ H ₁₄ BrN ₃ O ₂ :

Calculated . ..
found

C 54.85. H 3.79. N 11.29%; C 54.55. H 3.58. N 10.94%.

Example 28

4 g (0.0163 mol) of 2-methylamino are dissolved in 100 ml of benzene - 5 - chlorobenzophenone hydrazine dissolved. This solution is stirred and cooled with ice using 75 ml of 1 η sodium hydroxide solution were added. The resulting mixture is added dropwise at 0-5 ° C with 10 g (0.0495 mol) of bromoacetyl bromide were added. After the addition is complete, the mixture becomes 30 minutes touched. The acidic reaction mixture obtained is brought to a pH of about 8 with 1 η sodium hydroxide solution set. The temperature of the mixture increases without prior separation of the reaction product 10 to 15 C, and the mixture is then Stirred for 30 minutes. The benzene phase is then separated off in a separatory funnel. 3 times with Washed with water, dried over sodium sulfate and evaporated under reduced pressure. Of the ether is added to the oily residue, with 4 - bromoacetyl - 8 - chloro - 3.4 - dihydro - I - methyl-6- phenyl -1.4.5 -benzotriazocin - 2 (1 H) -one is obtained. After recrystallization from chloroformn-hexane white crystals with a melting point of 200 "C are obtained.

C ₁₁₁ H ₁₅ CIBrN ₃ O ₂ :

Calculated ... C 51.39. H 3.59. N 9.99%; found .... C 51.24. H 3.66. N 9.99%.

Example 29

36 g of 2-methylaminobenzophenone hydrazone in the form of an oil. by converting 37 g (0.175 Moll 2-methylaminobenzophenone is made with 100% hydrazine hydrate, will not crystallize, but dissolved in 500 ml of benzene. The solution was cooled while stirring and then treated with a Solution of 25 g (0.625 mol) sodium hydroxide in 750 ml water. The mixture is then Bend stirred while cooling with ice and then at 'to 10 C dropwise with 100 g (0.495 mol) of bromine acetyl bromide added. The reaction product is not isolated. When the addition is complete, there will be; The mixture was stirred at 10 to 15 ° C. for 1 hour. The acidic reaction mixture obtained is treated with 1N Na tron lye adjusted to a pH of about 8. The benzene layer is separated off, 3rr> al with water washed, dried over sodium sulfate and evaporated under reduced pressure. The concentrate ether is added, with 4-bromoacetyI-3,4-dihydro-1-methyl-6-phenyl-1,4.5-benzotriazocir 2 (1 H) -one obtained in the form of white crystals after recrystallization from chloroform-n-hexa white crystals from the r. 160 C.

The separation and purification of the reaction products :, can also be carried out in a simple manner by liquid chromatography des Kon / .cnlnits on silica gel (Eluent: benzene, ether, chloroform in a ratio of 1: 1: i).

C _ls H _u , BrN, O ₂ :

Calculated ... C 55.97. M 4.IS. N I0.SS "· ,,:
found .... C 5WW. II 4.00. N I0.5 ¹ ) ",,.

IO

Example 30

I. 10 g (0.0345 mol) of 2-amino-5-bromobenzophynonhydrazone are dissolved in 500 ml of chloroform. The solution is stirred while cooling with ice. A solution of 8 g (0.2 mol) of sodium hydroxide in 350 ml of water is then added to the solution, and the mixture is further stirred while cooling with ice. The mixture is then treated dropwise at 5 to 10 ° C. with 75 g of iO.37 mol) of bromoacetyl bromide. After the addition is complete, the mixture is continued at 10 to 15 ° C. for 1 hour. The reaction mixture is then adjusted to a pH of about 8 with 0.5N sodium hydroxide solution. The chloroform phase is separated off, washed with water, dried and evaporated under reduced pressure. Ether is added to the concentrate, 2 - bromoacetamido - 5 - bromobenzophenone bromoacelylhydrazone being obtained in the form of white crystals. After recrystallization from chloroform-ether-hexane, crystals of temperature 148 to 149 ° C. are obtained.

C ₁₇ H ₁₄ Br ₃ N ₃ O ₂ :

Calculated ... C 38.38. Il 2.65. N 7.90%:
found .... C 38.34. H 2.42. N 7.82%.

(0.4953 Moll Brom.icelylbromid added. After complete The mixture is added for 30 minutes stirred and then neutralized with I η sodium hydroxide solution. The chloroform phase is separated off with water washed, geiiocknct over sodium sulfate and under evaporated under reduced pressure. Ether is then added to the residue, with 2-bromacciamido - 5 - (luorbenzophenonbromoacetylhydni / on in 1-orm white crystals will emerge. After recrystallization Crystals were obtained from chloroform / hexane which replace at 154 to 156 ° C '.

C _n H ₁₄ Br ₃ FN ₃ O ₂ :

Calculated ... C 43.34. H 3.00. N 8.92%;
found .... C 43.06. H 2.88, N 8.78%.

2. 10 g (0.0256 moles) of 2-bromoacetate, ido-5-fluorobenzophenone bromacclyl hydrazone are dissolved in a mixture of 200 ml of chloroform and 2 (X) ml of acetone. This solution is then mixed with a mixture 50 ml of 0.5N sodium hydroxide solution and 50 ml of acetone are added. The resulting mixture is stirred. The organic phase is separated off, washed with water, dried over sodium sulfate and evaporated under reduced pressure. The concentrate comes with Ether added, with 4-bromoacctyI-6-phenyl-8-fluoro-3.4-dihydm-1.4.5-benzotriazoein-2 (l H) -one is obtained in the form of white crystals. After recrystallization Crystals are obtained from chloroform / hexane and decompose at 198.degree.

C ₁ -H ₁₁ BtFN ₃ O ,:

Calculated
found .

C 52.32. H 3.36. N 10.77%:
C 52.25. H 3.23. N 10.81%.

3 s

2. 10 si (0.018 minor of the 2-bromoacetamido-5-bromobenzophynonbromacclvlhydrazone prepared above are dissolved in 300 ml of chloroform. 240 ml of acetone are added to the solution. The mixture is then added dropwise with a solution of 0.7 g (0.019 mol) while stirring at room temperature Sodium hydroxide is added to 38 ml of water. The mixture is stirred at 30 ° C. for 2 hours and then mixed with water. The chloroform phase is separated off, washed with water, over sodium sulfate dried and evaporated under reduced pressure. The concentrate is made with a lower, Amount of benzene is added and the mixture is left to stand at room temperature, 4-bromoacetyl-3,4-dihydro-8-bromo-6-phenyl-1,4,5-benzotriazocin-2 (1 H) -one is obtained in the form of white crystals. After recrystallization from chloroform-ether-hexane Crystals with a melting point of 204 to 206 ° C are obtained.

C ₁₇ H ₁₃ Br ₂ N ₃ O ₂ :

Calculated ... C 45.26. H 2.90, N 9.31%:

found .... C 45.00. H 2.73. N 9.00%.

Example 31

1. 18 g (0.0785 mol) of 2-amino-5-fluorobenzophynonhydrazone are dissolved in 800 ml of chloroform. These 300 ml of 1 η sodium hydroxide solution are added to the solution while stirring and cooling with ice. Then will the mixture at 5 C dropwise with 100 g

Example 32

1. In 11 chloroform, 25 g (0.111 mol) 2-Amino-5-methylbenzophenone hydrazine dissolved, and the solution is cooled while stirring. The solution is then mixed with a solution of 10 g (0.25 mol) Sodium hydroxide in 250 ml of water is added, and the mixture is further stirred while cooling with ice. The mixture is then added dropwise at 5 to Λ) C. 7.5 g (0.37 mol) of bromoacetyl bromide were added. After the addition is complete, the mixture is 1 hour at Stirred at 10 to 15 C. The reaction mixture is with 0.5N sodium hydroxide solution adjusted to a pH of about 8. The chloroform phase is separated off, washed with water, dried over sodium sulfate and evaporated under reduced pressure. That Ether is added to concentrate, whereby 2-bromoacetamido - 5 - methylbenzophenonbromoacetylhydrazone is obtained in the form of white crystals. After recrystallization from chloroform -ether-hexane Crystals with a melting point of 142 to 143 C are obtained. c

C ₁₈ HpBr ₂ N ₃ O ₂ :

Calculated ... C 46.28, H 3.67, N 8.99%;
found .... C 46.00, H 3.48, N 8.79%.

2. 4.67 g of the 2-bromoacetamido-5-methylbenzophenone-bromoacetylhydrazone prepared above are placed in 60 ml of chloroform dissolved, and the solution is mixed with 100 ml of acetone. Afterward the mixture is stirred at room temperature, dropwise with a mixture of 100 ml

Acetone and an aqueous solution containing 0.4 g (0.01 mol) of sodium hydroxide in 20 ml of water, offset. The resulting mixture is stirred at room temperature for 30 minutes. The reaction mixture is then extracted with chloroform. Of the The extract is washed 3 times with water, dried over sodium sulfate and reduced under reduced pressure Pressure evaporated. A small amount of benzene is added to the concentrate and the mixture is then left to stand at room temperature, whereby 4-bromoacetyl-3,4-dihydro-8-methyl-6-phenyl-1,4,5-benzotriazocin-2 (1 H) -one is obtained in the form of white crystals. After recrystallization Crystals with a melting point of 211 to 212 ° C. are obtained from chloroform-ether-n-hexane.

C ₁₈ H ₁₆ BrN ₃ O ₂ :

Calculated .. C 55.97, H 4.18, N 10 88% ·
found .... C 55.72, H 3.92, N 10.66%.

20th

Example 33

A mixture of 50 g (0.1723 mol) 2-methylamino-5-bromobenzophenone and 200 ml of ethanol are mixed with 200 ml of ethanol saturated with hydrogen chloride. 500 g of 100% hydrazine hydrate are then added to the mixture. After adding 800 ml Ethanol, the mixture is refluxed for 7 to 8 hours while stirring. After cooling down the solution is extracted to room temperature with chloroform. The extract is made with water washed, dried over sodium sulfate and evaporated under reduced pressure. Here is 2 - methylamino - 5 - bromobenzophenone hydrazone obtained in the form of an oil. This oil is in 1 liter of benzene dissolved, and the solution is cooled with stirring. The solution is then mixed with a solution of 50 g (0.472 mol) of sodium carbonate in 1 l of water are added ", and the mixture obtained is with cooling with Keep stirring the ice. The mixture is then added dropwise at 5 to 10 C with 150 g of bromoacetyl bromide offset. When the addition is complete, the mixture is stirred at 10 to 15 ° C. for 1 hour. Afterward the pH of the mixture with 0.5N sodium hydroxide solution set to about 8. The benzene phase is separated off, washed with water, over sodium sulfate dried and evaporated under reduced pressure. The concentrate is then made with ether and a little benzene added, with 4-bromoacetyl-S-bromine -. ^ - dihydro-l-methyl-o-phenyl-M.S-benzo- triazocin-2 (l H) -one is obtained in the form of white crystals. After recrystallization from chloroform-ether-n-hexane Crystals with a melting point of 195 ° to 197 ° C. are obtained.

C ₁₈ H ₁₅ Br ₂ N ₃ O ₂ :

Calculated ... C 46.48, H 3.25. N 9.03%:
found C 46.33, H 3.03. N 8.71%.

55

60

Example 34

15 g (0.0654 mol) of 2-methylamino-5- (luorbenzophenone are mixed with K) OmI ethanol. This mixture is stirred with 60 ml with hydrogen chloride saturated ethanol added. The mixture obtained is, with cooling, with 150 g | 00 ° -'nigcm Hydrazine hydrate and then treated with 200 ml of ethanol. The mixture is stirred for 7 hours heated to reflux. The reaction mixture is cooled to room temperature and with chloroform extracted. The extract is washed 3 times with water, dried over sodium sulfate and taken under evaporated under reduced pressure. Here, 15 g of 2 - methylamino - 5 - fluorobenzophenone hydrazone are used obtained in the form of an oil. This oil is in 3 (X) ml Benzene dissolved and with a solution of 15 g (0.1415 mol) sodium carbonate in 250 ml! Water added. The mixture is stirred under a condenser. Subsequently, while the temperature is obtained Solution is kept at 5 to 10 C, this solution is added dropwise with 60 g (0.297 mol) of bromoacetyl bromide offset. When the addition is complete, the mixture is stirred at 10 to 15 ° C. for 30 minutes and then adjusted to a pH value of about 10 with 0.5N sodium hydroxide solution. The benzene phase is separated off, washed 3 to 5 times with water, dried over sodium sulfate and reduced under reduced pressure Pressure evaporated. The concentrate is mixed with a small amount of benzene and ether, where 4-bromoacetyl-8-fluoro-3,4-dihydro-1-meth \ l-6-phenyl - 1.4.5- benzotriazocin-2 (1 H) -one is obtained in the form of white crystals. After recrystallization from benzene ether crystals with a melting point of 143 to 144 ° C are obtained.

C _1n H ₁ jBrFW., 0 ,:

Calculated ... C J3.48. H 3.74, N 10.4%:
found .... C, 53.55. H 3.55, N 10.29%.

Example 35

A mixture of 50 g (0.222 mol) of 2-methylamino-5-methylbenzophenone and 200 ml of ethanol is mixed with 200 ml of ethanol and saturated with hydrogen chloride then mixed with 500 g of 100% hydrazine hydrate. The resulting mixture is then added with 9 (K) ml Ethanol is added and our reflux is heated for 7 to 8 hours. After the implementation is complete, the The reaction mixture was cooled to room temperature and chloroform was added. This mixture will Washed 3 times with water, and the chloroform phase is separated off and dried over sodium sulfate and evaporated under reduced pressure. This gives 2-methylamino-5-methylbenzophynonhydrazone obtained in the form of an oil. This oil is dissolved in 500 ml of benzene and the solution is taken under Cooled stirring. The solution is then treated with a solution of 25 g (0.625 mol) of sodium hydroxide in 1000 ml of water are added, and the resulting mixture is stirred while cooling with ice. Then will 150 g (0.743 mol) of bromoacetyl bromide were added dropwise to the mixture at 5 to 10 ° C. After full Addition, the mixture is stirred for 1 hour at 10 to 15 C and then with sodium hydroxide solution on one pH adjusted to about 8.5. The benzene phase is separated off. Washed 3 times with water. above Dried sodium sulfate and evaporated under reduced pressure. The concentrate is made with ether added, with 4-bromoacctyl-3,4-dihydro-1,8-dimethyl -6-phenyl-1.4.5-benzotriazocin-2 (1 H) -one in Form of white crystals is obtained. After recrystallization from chloroform-n-hexane, crystals become obtained from F. 189 to 191 C.

C 57.01. H 4.53. N 10.50%:
C 56.80. H 4.49, N 10.11%.

Calculated
found .

Claims (3)

Patent claims: 1. 1,4,5-Benzotriazocine derivatives and their salts the general form! I. R 'O N-C (I) in which X is a hydrogen or halogen atom or an alkyl radical, R 'is a hydrogen atom or a Alkyl radical and R ″ a hydrogen atom or the groupings -CO-CH ₁ -Y -CO-CH ₁ -N -CO-CH ₁ -N R ₃ R ₂ means wherein Y is a halogen atom. R _{1 is} a hydrogen atom, an alkyl or an allyl group and R _{2 is} a hydrogen atom. an alkyl. Allyl, anilino, benzyl, phenylethyl or phenyl group, the latter can be substituted by one or two methyl or ethyl groups or by a chlorine atom or a methoxy group, or R ₁ and R ₂ together with the nitrogen atom to which they are bound, a pyrrolidino, piperidino. Morpholino or piperazino group, and R ₃ denotes an alkyl group or R ₁ , R ₂ and R ₃ together with the nitrogen atom to which they are attached form a hexamethylenetetramine group, the alkyl radicals being understood to be those with 1 to 4 carbon atoms. 2. Process for the preparation of the benzotriazoein according to claim 1, characterized in that that in a known manner a benzophenone hydrazone of the general formula II R '
NH (II) 55 60 --N-NH, genids of the general formula HI Y - CO - CH ₂ - Y (IH) converts and the reaction product of the general formula IV N-COCH ₂ Y (IVi C = N-NHCOCh ₂ Y cyclized without prior isolation and optionally the reaction product of the general formula V R O N-C / V CH, (Vi N-COCH ₁ Y C = N a) for the preparation of compounds in which R 'denotes a hydrogen atom, with a base deacylated or bl for the preparation of compounds in which R the groupings R. CO-CH ₂ -N or R ₁ -CO-CH ₂ -N means with an amine of the general Formula VI or VII H - NR, R ₁ N --- R, (VIl (VII) reacted with at least 2 moles of a halotiene acetyl halo. 3. Medicinal preparations consisting of a ben / .utriuzocin according to claim I and customary auxiliaries. moniumuceiyl and N-methylpiperidinium aetyl group. The invention also relates to a method for Hcr- position of the 1,4,5-Beiuotriazocinderivuie the general my formula I. which is characterized by it. that in a known manner a benzophenone hydrazone of the general formula II The invention relates to 1,4,5-Benzüiriazodnderivate and their salts of the general formula I. R 'O N-C (D NH C = N-NH ₂ (II) with at least 2 moles of a haloacetyl halide of the general formula III in which X is a hydrogen or halogen aiom or an alkyl radical, R 'a hydrogen atom or a Y-CO-CH ₂ -Y (III) Alkyl radical and R "is a hydrogen atom or the Reacts groupings and the reaction product of the general 30 shapes! IV -CO-CH ₂ -Y - CO - CI, - N R ₂ R ₁ R ' N-COCH ₂ Y = N-NHCOCH ₂ Y uv: -CO-CH ₇ -N means wherein Y is a halogen atom. R _{1 is} a hydrogen atom. denotes an alkyl or an allyl group and R ₂ denotes a hydrogen atom, an alkyl, allyl, anilino, benzyl, phenylethyl or phenyl group, the latter being substituted by one or two methyl or ethyl groups or by a chlorine atom or a methoxy group or R ₁ and R ₂ together with the nitrogen atom to which they are bonded form a pyrrolidino, piperidino, morpholino or piperazino group, and R _{3 is} an alkyl group or R ₁ , R ₂ and R ₃ together with the The nitrogen atom to which they are bonded form a hexamethylenetetramine group, the alkyl radicals being understood to be those having 1 to 4 carbon atoms. If in the general formula IX and Y denote a halogen atom, this halogen atom can be a chlorine atom. Be bromine, fluorine or iodine alom. If X. R '. R ₁ , R ₂ or R ₁ denote an alkyl radical, this alkyl radical can be straight-chain or branched. Special alkyl radicals are the methyl. Ethyl-. Propyl, isopropyl. Butyl or isobutyl group. Specific examples of R ″ are the aminoacetyl, methylaminoacetyl, dimethylaminoacetyl, trimethylamino cyclized without prior isolation and optionally the reaction product of the general formula V R 'O N-C CH ₂ N-COCH ₂ Y (V) al for the preparation of compounds in which R "denotes a hydrogen atom, with e.r.cr base cntacylicrl or