IL41277A - Dibenzotriazolo-azepines,-diazepines,-oxazepines and -thiazepines - Google Patents

Description

Dibenzotriazolo-azepines ,-diazepines-oxaze pines and thiazepinea ABSTRACT OF THE DISCLOSURE Compounds of the formula I I I : wherein X is selected from the group consisting of oxygen sul in which R5 and Re are each selected from the group consisting of hydrogen and alkyl of 1 to 3 car- bon at o: , inclusi e , «««}— W-Ji^ > N-R-, in which R, is hydrogen; in which n is .1 to 4, inclusive, rind !' s al yl defined ns above, or and are each selected fron the proup consisting: of hydrogen and alkyl as defined above or -K together is pyrrol ino, and iperidino; wherein li? lias the sn::c s i <. n i ficancc as 41277/3 consisting of hydrogen and chloro, are prepared by reacting a thlo compound of formula I: wherein X, R^, and are defined as above, 1n sequence: 1. with an al ylcarbazate; and the resulting product II 2. with an aiKylating agent of the formula R^ I 1n which 21s defined as above, to obtain a compound III as defined above.

BACKGROUND OF'THE INVENTION Fl ELD OF THE I VENTI ON This invention is directed to new organic compcund 5" and is particularly concerned with novel compounds I I an I I I and a process for the production thereof.

The novel compounds and the process of production therefor can be i l lustrati ely represented as fol lows : whe sul gr atoms, inclusive; and in hich Ra is selected i'rom the group consisting of hydrogen, - 41277/2 -·ν wherein η 1s 1 to 4, Inclusive, and R 1s alk l defined as above or R, 1s 1n which R, and R0 are selected from the group consisting of hydrogen and alkyl as defined above and n 1s defined R7 as above; or together 1s pyrrol 1d1 no, and¾p1per1d1no, wherein '8 or it is (benzylmethylamino) ethyl, has the same significance as R^/and wherein R3 and R^ are selected from the group consisting of hydrogen and chloro.

The Invention also embraces the pharmacologically acceptable add addition salts TflOTOoT of the compounds of formula III above.

The process of this Invention comprises heating a thlo compound of formula I with an alkyl carbazate to obtain the triazolone compound II and al ylatlng II with a compound of formula C1R2* BrRg, of 1 21n which Rg 1s defined as above to produce a compound of formula III above.

DESCRIPTION OF THE PREFERRED EMBODIMENT Lower alkyl groups of 1 to 3 carbon atoms, Inclusive, are exemplified by methyl, ethyl, propyl, and Isopropyl.

The group CnH2n wherein n is 1 to comprises -CH2--(CHa)2-, -(CH2)3-, -(CH2)4-, and branched alkylene such as The novel compounds of formula M l and pharmacological ly acceptable acid addition salts thereof have antidepressant activity and are thus useful for the treatment of depression, in mammals or birds.

The main function of an ant i -depressant is 'to return the depressed individual up to normal function. This should be careful ly differentiated from psychic stimulants such as the amphetamines which produce over timulation in the normal individual.

Many different methods have been and are used to evaluate antidepressant activity. In general these methods involve antagonism to a depressant such as reser-pinc or tet rabenaz i ne or a synergistic increase of the toxicity of certain compounds (i .e. yohimbine or ~5 ,K-d i hyd roxypheny 1 a 1 an ϊ ne ) and comparison of the drug action of the new compound with other known ant ?de ressants . No single test alone can determine whether or not a new compound is an antidepressant or not, but the profi le evidenced by various tests wi ll establish the ant i -depress -ant action if present. A number of such tests are described below.

Hypothermic tests with oxot remor i ne^ [ 1- [4- (pyrrol - i d i ny 1 ) -2-but yny 1 ] -2-py r ro*l i d i none ] .

Oxotremorine (as wel l as apomorphine and tetrabena- 2932 A ^ zine) produces hypothermic responses in mice. This response is blocked by antichol inergics and ant i - dep ress -ants such as atropine and imipramine.

Oxotremorine produces a very pronounced hypothermia which reaches a peak 60 minutes after administration.

At 0.6 mg./kg. the body temperature of a mouse is decreased about 13° F. (when the mouse is kept at room temperature). This temperature decrease is antagonized by ant i -depressants e.g. desipramine, imipramine, doxe-pine, and others as can be seen from Table I .

TABLE I Effect of Various Compounds on Oxot remor i ne- I nduced Hypothermia in Mice Oose Body Temperature °F-Change mg./kg., Absorption From Vehicle Control After Compound I . P. Time (min) Minutes 30 60 90 oxot remor i ne (Control ) 0.6 -5.8 -11.6 -13.2 - 8.0 Des ί pra-m i ne 25 30 -3.5 - 3.5 - 4.1 - 3.6 I m i pra- 25 30 -0.4 - 3.3 - 5.6 - 6.4 m i ne I pr i n-do 1 e 25 30 -6.3 -11.8 -12.8 -11.9 Ooxe-p i ne 25 30 -2.3 - 7.1 -11.0 -12.3 Ami tr i p-ty 1 i ne 25 30 +0.7 - 2.4 - 5.4 - 6.8 Ampheta-m i ne 5 30 -1.5 - .3 - 4.4 - 2.2 r + - - - The present compounds were tested as follows. Four male mice of 18-22 g. (Strain CF=Carworth Frams ) were injected i nt raper i tonea 11 y with 1 mg . of oxotremori ne .

The lowering of the body temperature was measured rectal ly with an electronic theremometer , before and 30 minutes after drug administration. After the drug administration o the mice were kept at 19 C. in cages.

The results are tabulated below: TABLE I I Average body temperature of mice in Fahrenheit degrees Vehicle (control ) 101 oxotremorine (l mg.) 83.8 oxotremorine (l mg.) and A (100 mg.) 93.3 oxotremorine (l mg.) and B (100 mg.) 89-5 oxotremorine (l mg.) and C 88.1 A = 2-[2- (dimethylamincjethyl ¼-2 , 9-d i hydro-3H-d i benzoic c, f] -s-tr iazolof^, 3_a]azepin-3~one B = 2- [2- (d imethy lam i no)propy 1 ] -2 , 9-d i hydro-3H-d i benzo-[bJf]-s-triazolo[4.3-d] [l, ]d iazepi n-3-one ; C = 2- [2- (dimethylamino)propy 1 ]-2J9~dihydro-3H-dibenzo-[c,f] - s-tr iazolo[4-,3-a]azepin-3- one; Potentiation of yohimbine aggregation toxicity: the LD5o of yohimbine hydrochloride in mice is 5 mg./kg. i .p. Administration of 30 mg./kg. of yohimbine hydrochloride was non-lethal . I f an antidepressant is administered prior to the yohimbine hydrochloride (30 mg . ) the lethal ity of the yohimbine hydrochloride is increased.

Ten male CF mice, 18-22 g., were injected with yohim- The LD50 are determined. Groups of ten mice are injected with the antidepressant 30 minutes before the administration of yohimbine hydrochloride [YCl] (30 mg.). No mice or only one mouse is ki lled from 30 mg . of [YCl]. I f [YCl] is administered in the presence of an ant i -depressant an increase in the toxicity of [YCl] is found. The ED50 value of the three compounds A, B, and C in causing 50$ of the mice to die is shown in Table I I I : TABLE I I I [YCl] (30 mg. ) control no deaths [YCl ] (30 mg. ) and A 7 mg. (A) [YCl] (30 mg. ) and B 16 mg. (B) [YCl ] (30 mg. ) and C 40 mg. (C) Potentiation of apomorphine gnawing: a group of 4 mice (male, CF, 18-22 g.) are administered the test compound i nt raper i tonea 11 y one hour prior to the subcutaneous injection of apomorphine hydrochloride 10 mg./kg. The mice are then placed in a plastic box (6" x 11" x 5") lined at the bottom with a cel lophane-backed,, absorbent paper. The degree of damage to the paper at the end of 30 min. is scored from zero to . The scores 3 and indicate that the compound is a potentiator of apomorphine in this test. All 3 compounds. A, B, and C, were positi e in this test at 100 mg./kg. in mice.

Thus, the above results show that compounds of formula I I I and the pharmacologically acceptable acid addition salts aR€l-- — ex-i-des thereof can be used as antidepressants in mammals to achieve normalcy in the depressed individual N-oxides, and salts thereof contem lated by this invention include pharmaceutical compositions suited for oral, parenteral, and rectal use, e.g., tablets, powder packets, cachets, dragees, capsules, solutions, suspensions, steri le injectable forms, suppositories, bougies, and the l ike.

Suitable di luents or carriers such as carbohydrates, lactose, proteins, lipids, calcium phosphate, cornstarch, stearic acid, methy 1 ce 1 lu 1 ose and the like may be used as carriers or for coating purposes. Water or oi ls such as coconut oi l, sesame oil, saff lower oi l, cottonseed oi l, and peanut oi l, may be used for preparing solutions or suspensions of the active drug. Sweetening, coloring and flavoring agents may be added.

For mammals food premixes with starch, oatmeal, dried fishmeat, fishmeal, flour, and the like can be prepared.

As antidepressants the compounds of formulae I I and I I I their pharmacologically acceptable acid addition salts can be used in dosages of 0.1-5 mg./kg. in oral or injectable preparations as described above to al leviate depression occurring in stressful situations. Such situations are those for example, when animals are changing ownersh ips or are temporari ly put into kenne^l whi le their owners are absent from home.

Acid addition salts of the compounds of formula I I I can be made, such as the fluosi licic acid addition salts which can be appl ied as mothproofing agents, and salts with trichloroacetic acid are useful as herbicides against Johnson grass, Bermuda grass, yel low and red foxtai l, 2932 A r The starting materials of this invention are dihydro-d i benzoazep i neth i ones I which are either known or can be synthesized, for simplicity by treating the corresponding oxo compounds with phosphorus pentasul ide as further i llustrated by the Preparations 1 and 7.

In carrying out the process of this invention, a selected thione I , is heated with an a 1 ky 1 carbazate of the formula: HaN-NH-COOAlk in which the a 1 ky 1 group is of 1 to 3 carbon atoms, inclusive. Usually ethyl carbazate is preferred, but higher alkyl carbazates are operative. In the preferred embodiment of this invention, the selected thione I is heated with ethyl carbazate in large excess for 1/2 hour to j3 hours at 190 to 250° C. in an oi l bath. The alkyl carbazate serves simultaneously as reagent and solvent. The product usually precipitates upon cooling of the reaction mixture and is recovered by fi ltration and purified by conventional means, e.g., extractions of impurities, chromatography or most commonly by recrysta 11 i zat i on. The triazolone compound I I is thus, obtained.

Alkylation of I I is achieved by reacting the product I I with a strong base e.g. sodium or potassium hydride in an organic solvent, e.g. d i methy 1 for mam i de , diethylfor-mamide, d iethy lacetamide, tetrahydrofuran, dioxane, benzene or the like with an excess of the base, fol lowed by reacting the alkali metal salt thus formed with R2X in which X is chlorine, bromine, or iodine and R2 is defined as above. Both reactions, formation of salt and the reaction of this 2932A r ^4 tures between 50 to 125 C. The conversion of I I to its alkal i salt is usually performed during 15_75 minutes.

The reaction of the salt with the chloride is carried out during a longer period of time by keeping the reaction mixture at the elevated temperature for 1 to >6 hours.

The product I I I, thus obtained, is isolated and purified by conventional means e.g. extraction, chromatography, crystal lization and the like.

The following preparations and examples are i l lustra-tlve of the processes and products of the present invention, but are not to be construed as limiting.

Preparation 1 6 (5H ) -morphanth r i d i neth i one A mixture of 6 (5H ) -morphanthr i d i none (30 g., 0.144 mole), phosphorus pentasulfide (33-5 g · .> 0.158 mole) and 1200 ml. of pyridine was heated at reflux temperature for 23 hours and the pyridine was then evaporated. Methylene chloride and water were added, and the organic layer was separated (some sol id was present), washed with aqueous sodium bicarbonate unti l only a trace of solid was present, then with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. Trituration of the residue with methanol gave 28.8 g. of 6(5H)-mor-phanthr id i neth i one, of melting point 2l8-2l9° C. Crystallization from methylene ch 1 or i de-methano 1 gave the pro-duct as pale yellow rods; the melting point was unchanged. Ana 1. calcd. for C14H11 2 : C, 7^.63; H, 4.92; N, 6.22; S, 14.23.

Found: C, 74.94; H, 5.07; N, 6.08; S, 14.25.

Preparation 2 5 , 10-0 i hyd ro- llH-d i benzo[ b, e ] [l,4]d i azepi ne- 2932 A A mixture of 5 , 10 -d i hyd ro- llH-d i benzo[b ,e ] [ 1, ] d i aze-pin-ll-one (10 g., 0.0476 mole), phosphorus pentasu lfide (9-3 9·, Ο.Ο525 mole) and 365 ml . of pyridine was heated at reflux temperature for 3 hours and al lowed to stand overnight. The pyridine was evaporated, and the residue was shaken with 250 ml . each of water and chloroform.

The resulting suspension was fi ltered to remove sol id product. After fi ltration the chloroform layer was separated from the aqueous layer, washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. The residue was combined with the sol id obtained above and crystal l ized from methanol . Two crops of 5,10-d i hydro- llH-d ibenzo[b,e] [l,4]diazepin-ll-thi one were obtained; yield, 9.01 g. (84$ of theory), melting poi nt 257-2 9° C.

Preparation 3 Dibenzo[b, f J [ 1 , 4] oxaze i ne-11 (lH)-thione A mixture of d i benz [b, f ] [1 , 4 ] oxaze i n- 11 (lOH ) -one (21.6 g. , 0.1 mole), phosphorus pentasulfide (23.4 g., 0.105 mole) and 850 ml . of pyridine was heated at reflux temperature for 4 hours and the pyridine was evaporated in vacuo. The residue was sti rred with chloroform, and 500 ml . of saturated aqueous sodium bicarbonate solution was added. The resulting suspension was fi ltered and the sol id was discarded. The fi ltrate was separated into layers, and the organic layer was washed successively with aqueous sodium bicarbonate and with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. The residue was crystal lized from ch 1 o roform-methan-ol ; 14.6 g. of d ibenzo[b, f] [l,4]oxazepi ne-11 (lOH)-th ione 2932A - 19^-195 C. Recrystal 1 ization did not alter the melting poi nt .

Ana 1. calcd. for C13H9NOS : C, 68.69; H, 3-99; N, 6.16; S, l4.ll.

Found: C, 68.50; H, 3-93; N, 6.30; S, 13-77.

Preparation 4 Dibenzo[b, f] [1 , 4] th i azepi ne-11 (10H ) - th i one A mixture of d i benzo[b , f , ] [ 1 , 4] th i azep i n- 11 (10H ) -one and phosphorus pentasulfide in pyridine was heated at reflux for 6 hours. The pyridine was evaporated in vacuo and the residue was processed as in Preparation 2 to give d i benzo[b, f ] [1, 4] thiazepi ne-11 (lOH)th i one ; melting point 246-247.5° C.

Preparation 5 7~ Ch loro-5 , 10-d i hyd ro-llH-d i benzo[b ,e ] - ~ [l,4]d iazepi ne-ll-thione A mixture of 7~ch 1 oro-5 , 10-d i hydro- llH-d i benzo[b, e ] -[l,4]diazepin-ll-one (30.5 g., 0.125 mole), phosphorus pentasulfide (27.8 g., 0.131 mole) and one 1. of pyridine was heated at reflux temperature for 4 hours and the pyri-dine was evaporated in vacuo. The residue was stirred for 1 hour with one 1. each of saturated aqueous sodium bicarbonate and methylene chloride and fi ltered to remove some solid product. The organic layer of the fi ltrate was washed successively with sodium bicarbonate solution 2932A nes ium su l fate and evaporated. The res idue was combined with the sol id obtained above and triturated with hot ch loroform and methanol ; 12.2 g. of 7-ch 1 oro-5 , 10 -d i hyd ro-llH-d i benzo[b , e ] [ 1 , 4]d i azep i ne- 11- th i one was obtained ; melt ing point 274-275° C. Concentration of the chloroform methanol washings afforded an additiona l 8.4 g. of product having the same melting point . Recrysta 11 i zat i on from d imethy 1 formamide-water gave an analytical sample in the form of pale yel low needles of melting point 276-277° C. Preparation 6 5, 10-D i hyd ro-5-methy 1 -llH-d ibenzo[b,eJ - [l,4]diazepine-ll-thi one A mixture of 5 , 10-d i hydro-5_methy 1 -llH-d ibenzo[b, e] - [l,4]d iazepi n-ll-one (6.1 g. 0.0272 mole) , phosphorus pentasu l fide (6.51 g., 0.0286 mole) and 175 ml . of pyri -dine was heated at reflux temperature for 3-75 hours and the pyridine was then evaporated in vacuo. The res idue was shaken with chloroform and saturated aqueous sodium bicarbonate. The resu lting suspension was fi ltered to give sol id A. The chloroform layer of the fi ltrate was washed successively with saturated aqueous sodium bicarbonate and with saturated salt solution, dried over anhydrous magnes ium sul fate and evaporated. The res idue was crysta l l ized from methylene ch 1 or ide-methano 1 to give 3.5 g. of 5J10-dihydro-5-methyl-llH-dibenzo[b,e] [l, ]diazepin-11-thione of melting point 217-218° C , which was unchanged after recrysta 11 i zat i on . A second crop wei ghed 0.8 g. and melted at 214-215° C.

Sol id A was shaken with methylene chloride and 10$ sodium hydroxide and processed as above to give an addi - Ana 1. calcd. for C14H12 2S: C, 69.96; H , -5.'30 ; N, 11.66; S, 13.3 ; N, 11.66. Found: C, 69-79; H, 5.20; N, 11.37; S, 13. 9. -Preparation 7 2- Ch loro-6 (5H) -morphanthr id i neth ione A mixture of 2-ch 1 oro-6 (5H ) -morphanth r i d i none (10 g. 0.046 mole) phosphorus pentasu 1 fi de (11.2 g.) and 340 ml. of pyridine was refluxed 3 hours and evaporated in vacuo. The residue was stirred for 2 hours with 500 ml. of methy ene chloride and 250 ml . of saturated salt solution, drie and evaporated. The residue was combined with product A and crystal lized from ch 1 or of orm-methano 1. Two crops of 2-ch 1 oro-6 (5H ) -morphanthr id i neth i one were obtained: a first crop of 5-6 g. in the form of yel low needles of melting point 246-257.5° C, and a second of 4.0 g. of melting point 245-246° C. ; yield, 93$ Ana 1. calcd. for Ci4Hi0ClNS: C, 64.73; H, 3.88; CI, 13.65; , 5-39; S, 12.35.

Found: C, 69.66; H, 3.83; CI, 13.89; N, 5-38; S, 12.05. Other starting materials of formula I are produced as shown in the preceding Preparations. Such starting materials include: ' ,8-d i ch 1 oro-6 ( H ) -mo rphanth r i d i neth i one ; 41277/2^ >8-dichloro-5>10-dihydro-llH-dibenzo [b,e][l,4] diazepine-ll-thione; and the 1 i ke .

Example 1 2i9-dihydro-3H-Dibenzo[c,f]-s-triazolo[ ,3-a]-azepin-^-one A mixture of 6 (5H ) -morphanth r i d i neth i one (2.8.8 g. , 0.128 mole) and ethyl carbazate 033 g . * 1.28 mole) was heated in an oi l bath preheated to 195-205° using a takeoff condenser (45 ml . was removed). The resulting sol id was- mixed with methylene ch lor i de- water and the suspension was fi ltered to give 12.6 g. of 2 , 9-d i hyd ro- 3H-d i benzo-[c f j-s-triazolo[4;>3-aJazepin-3-one melting at 276-279° C. The fi ltrate was separated into layers, and the organic layer was washed with water and saturated salt solut ion and dried over anhydrous magne ium su lfate. About half of ■the solvent was removed by disti l lation and the solution was a l lowed to stand;' 2.6 g. of product melting at 288-29C C. separated. An addit ional crop of 3-3. g. melting at 285- 88° C. was also obtained. Al l crops of product were combined and crystal l ized from methylene chloride; yield 14.2 g. (44$) melting point 289-29Ο0 C, unchanged on recrystal 1 izat ion.

Ana 1. calcd. for Ci5Hi iN30: C, 7 .27; H, 4.45 ; , 16.86.' Found: C, 72.20; H , 4.30; N, 17.17.

Example 2 2- [2- (0 i me thy lam rno) ethy l]-2,9-dihydro-3H-d i benzol c, f ] - s - tr ia ol o[ 4,3-a ]azep i n-3-one 2952 A d ro-3H-d i benzo[c, f ] -s- 1 r i azo 1 o[4,3~a Jazepi n-3_one (2. 9 g., 0.01 mole) in 100 ml. of d i methy 1 formam i de and the mixture was heated at 95° for 30 minutes. The mixture was cooled to 50° C. and a solution of d imethy lami noethy 1 chloride (l.07 g., 0.01 mole in 1.07 g. of xylene) was added. The mixture was heated at 95° C. for l8 hours and evaporated. The residue was taken up in methylene chloride-water and extracted with methylene chloide. The extract was washed with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. Crystal lization of the residue gave 2 g. of colorless prisms of 2- [2- (d inne thy lami no) ethyl ] -2 , 9-d i hyd ro-3H-d i benzo[ c, f] -s-tr iazolo[4,3~a Jazepi n-3-cn e, melting point, l6l-l62° C. which was unchanged on recrys ta 11 i zat i on of the product. A second crop of 200 mg . melting at l6l-l62° C. was obtained.

Ana 1. calcd. for C19H20N4O: C, 71.22; H, 6.29; N, 17. 9.

Found: C, 71.20; H, 63.4; N, 17.33.

Example 5 2 - [3- (d i methy lam i no)propy 1 ] -2 , 9-d i hyd ro-3H-dibenzo[c,fJ-s-triazolo[4,3-a]azepi n-3-one Sodium hydride (O.I78 g., 4.21 mmoles of a 57$ dispersion in mineral oi l) was added to a solution of 2,9-di-hyd ro-3H-d i benzo[c, f ] -s- 1 r iazol o [4,3- a Jazepi n-3-one (l .05 g. 4.21 mmoles) in 50 ml. of d imethy 1 formam i de and the mixture was heated at 95° C. for 35 minutes. The mixture was cooled to 50° C, a solution of 3"d i methy lami nopropy 1 chloride (0.51 g., 4.21 mmole in 0.51 g. of xylene) was added and heating was continued at 95° C. for 21 hours. 2932 A ί added to the residue. The organic layer was separated and extracted three times with 10 ml. portions of 10^ aqueous hydrochloric acid. The acid extract was cooled, made alkaline with 15$ aqueous sodium hydroxide and the basic mixture was ext racted wi th methy 1 ene chloride. The extract was washed with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. Crystallization from ether of the residue gave 0.975 g. of 2- [3- (d i methy lam i no) propyl ] -2 , 9-d i hyd ro~3H-d i benzo- [ c, f]-s - t r i azo 1 o[ 4, 3_a Jazep i n-3- one of melting point 130-131° C, unchanged on recrysta 11 i zat i on .

Ana 1. calcd. for C20H22N4O: C, 71.83; H, 6.63; N, 16.76.

Found: C, 71.91; H, 6.63; N, 17.16.

Example 4 2- [3- (4-methy 1 -1-p i peraz i ny 1 )propy 1 ] -2 , 9-d i hy-dro-3H-d i benzo[c, f ] -s - tr iazol o[ , 3-a]azepi n-3-one and its d i hyd roch 1 or i de Sodium hydride (0.42 g., 0.01 mole of a 57$ dispersion in mineral oil) was added to a solution of 2,9-dihy-d ro-3H-d ibenzo[c, f ] -s - t r iazol o[4,3-a Jazep i n-3-one (2.49 g., 0.01 mole) in 100 ml. of d i methy 1 formam i de and the mixture was heated at 95° C. for 30 minutes. The mixture was cooled to about 50° C. A solution of 1- (3-ch 1 oropro-py 1 ) -4-methy 1 pi peraz i ne [prepared according to F. Sowinski and H. L. Yale, J. Med. Chem., 5 (1962)] (1.76 g., 0.01 mole in I.76 g. of xylene) was added and the mixture was heated at 95° C. for 21 hours. The mixture was evaporated the resulting residue was dissolved in methylene chloride-water. The organic layer was separated and 2932 A extract was cooled, made alkaline with 1 $ aqueous sodium hydroxide and the basic mixture was extracted with methylene chloride. The extract was washed with saturated salt solution., dried over anhydrous magnesium sulfate and evap-orated to give 2- [3_ (4-meth 1 - 1- p i peraz i ny 1 )p ropy 1 ] -2 , 9-dihydro-3H-dibenzo[c,f]-s-triazolo[4,3~a]azepin-3-one. The residue was dissolved in ether, treated with 100 ml. of 1 hydrogen chloride in ethanol, and the resulting gum was crystallized from methanol -ether to give 2.9 g. of 2-[3- (4-methy 1 -1-pi perazinyl ) propy 1 ] -2 , 9-d i hyd ro-3H-d i benzo[c,.f ] -s-tr iazolo[4,3-a]azepin-3-one d i hydrochloride partially hydrated, of melting point 277-2790 C, (dec), raised to 279-281° C. on recrys ta 11 i zat i on .

Anal . calcd. for C23H2yN50-2HCl . l/4H20; C, 59.16; H, 6.37; N, 15.00; CI, 15.19- Found: C, 59-17; H, 6.45; N, 15.14; CI, 15.07.

The anhydrous product is obtained by drying the hydrate at 100° C. in vacuo for several hours.

Example 5 2 , 9-0 i hydro-3H-d i benzo[b , f ] -s- t r i azo 1 o[4, 3-d ] -[ 1, 4] d i azep i n-3-one A mixture of , 10-d i hyd ro-llH-d i benzo[b, e ] [ 1 , 4] d i aze-pin-ll-thione (21 g., 0.093 mole) and 100 g. of ethyl car-bazate was heated for 50 minutes at 190-200° C. in an oil bath preheated to that temperature using a take-off con-denser. During this time 25 ml. of liquid was removed.

The mixture was cooled to 50° C. and 100 ml . of water was added. The resulting suspension was filtered and the solid was washed with water and ether. The 2,9-dihydro-3H-dibenzo[b,f]-s-t riazolo[4,3"d] [l,4]diazepin-3_one thus 2932 A 262-2β3.5 C. after recrys ta 11 i za t i on from acetone- water- the melting point was 263-264.5° C.

Ana 1. ca 1 cd . for Ci4HioN40: C, 67.19; H, 4.03; N, 22.39.

Found-. c, 66.79; H, 3-96; N, 22.43.

Example 6 2- [2- (D i methy 1 am i no) ethy 1 ] -2 , 9-d i hydro-3H-dibenzo[b,f]-s-triazolo[4,3-d][l,4]diazepine-3-one Sodium hydride (0.456 g., 0.0108 mole of a 57$ dispersion in mineral oil ) was added to a solution of 2,9-dihydro-3H-dibenzo[b, f ] -s - 1 r i azo 1 o[4 , 3-d ] [ 1,4] diazep intone (2.7 g., O.OIO8 mole) in 95 ml. of d i methy 1 formam i de and the mixture was heated at 95° C. for 30 minutes. The mixture was cooled to 40° C. and a solution of 2-dimethyl-aminoethyl chloride (l.l6 g. ; 0.0108 mole in 1. l6 g. of xylene) was added. The mixture was heated at 95° C. for l8 hours and evaporated. Water and methylene chloride were added the organic layer was separated and extracted three times with 20 ml . portions of 10<& aqueous hydrochloric acid. The' acid extract was washed with ether and the ether was discarded. The extract was cooled, made alkal ine with 15$ aqueous sodium hydroxide and extracted with methylene chloride. The extract was washed with water and with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. The residue was crystal lized from ether to give I.83 g. of small, tan prisms of 2- [2- (d imeth 1 ami no)ethy 1 ] -2, 9-d i hyd ro-3H-d i ben-zo[b, f ] -s - t r i azol o[4,3-d ] [ l,4]d iazep i n-3-one of melting point 143-144. ° C. After recrys ta 11 i zat i on the melting point was 144-145° C. 2932 A C, 67.27; H j 5.96; N, 21.79.

Found: C, 67.25; H, 6.10; N, 21.44.

Example 7 2- [3- (Dimethy lam i no) p ropy 1 ] - 2,9-d i hydro- 3H-di enzofb^fj-s-triazolot^^-djfl^jdiazepi n-3-one Sodium hydride (0.456 g., 0.0108 mole of 57 dispersion in mineral oi l) was added to a solution of 2,9-dihy-d ro~3H-d i benzo[b, f]-s-triazolo[4,3-d][l,4]diaze in-3-one (2.7 g., 0.0108 mole) in 95 ml. of d i methy 1 formam i de . The mixture was stirred at room temperature for 30 minutes and then heated at 95° C. for 30 minutes. The mixture was cooled to 40° C, a solution of 3_d i methy 1 am i nopropy 1 chloride (l.31 g., 0.0108 mole in 1.31 g. of xylene) was added and heating at 95° C. was continued for 21 hours. The mixture was concentrated by disti llation and water and methylene chloride were added to the concentrate. The organic layer was separated and extracted three times with 20 ml . portions of 10$ aqueous hydrochloric acid. The acid extract was washed with ether (which was discarded) made alkaline with 15$ aqueous sodium hydroxide and the basic mixture was extracted with methylene chloride. The extract was washed with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. The residue was crystal l ized from ether to gi e 2.5 g. of 2-[3- (d i methy lam i no) propyl ] -2 , 9-d i hydro-3H-d i benzo[b, f ] -s-t riazolo[4,3-d] [l, ]d iazepi n-3-one, melting point 125 -126° C.

Ana 1. calcd. for Ci9H2iN50: C, 68.08; H, 6.31; N j 20.88.

Found: C, 68.20; H, 6.42; N, 20.73. 2932 A py l]-3H-dibenzo[b,f ]-s-triazolo[ ,3-d] [l, ]diazepin-3-one and its d i hyd roch 1 or i de Sodium hydride (0.456 g., 0.108 mole of a 57^ dispersion in mineral oi l ) was added to a solution of 2,9-dihy-dro-3H-di benzo[b, f]-s-triazolo[4,3_d][l,4]diazepi n-3-one (2.7 g . , O.IO8 mole) in 95 ml . of dimethyl formamide and the mixture was heated at 95° C. for 30 minutes. The mixture was cooled to 40° C, a solution of 1- (3-ch loropro-py 1 ) -4-methy 1 p i peraz i ne (1.9 9·> 0.0108 mole in 1.9 g. ; of xylene) was added and heating at 95° C. was continued for 22 hours. The mixture was evaporated. The thus -obta i ned residue was dissolved in methylene chloride and water. The organic layer was separated and extracted three times with 10 ml . portions of 10$ aqueous hydrochloric acid. The acid extract was washed with ether (which was discarded), cooled, made alkal ine with 1 ^ aqueous sodium hydroxide and the basic mixture was extracted with methylene chloride. The extract was washed with water and with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated to dryness. The 2 , 9-d i hyd ro-2 - [3-(4-methyl-l-piperazinyl ) propy l]-3H-dibenzo[b,f]-s-triazo-lo[4,3-d] [l,4]diazep in-3-one thus obtained was dissolved in 30 ml . of methanol and added to 100 ml . of 1.1. _N ethereal hydrogen chloride. The gum which separated was triturated with hot methanol, yielding 2.4 g. of 2,9-dihydro-2-[3- (4-methyl-l-piperazinyl ) propy 1 ] -3H-d i benzo-[b,f]-s-triazolo[4,3-d] [l,4]diazep i n-3-one d i hyd roch lor i de of melting point 288-290° C. After crystal l ization from methanol -methy lene chloride the product melted at 286-288° 2932A AnaJ.. calcd. for C22H27Ne0-2HC 1 : C, 57-02; H, 6.09; C 1 , 15-30; N, 18.14.

Found: C, 56.99; H, 6.25; CI, 15-08; N, 18.44.

Example 9 5" (3-d i methy 1 ami nop ropy 1 )-5,10-dihydro-llH-dibenzo[b,e][l,4]diazepin-ll-thione A mixture of 5_ (3-d i methy 1 ami nop ropy 1 ) -5 , 10-d i hyd ro-HH-dibenzo[b,e] [l,4]diazepin-ll-one (5 g., 0.017 mole), phosphorus pentasulfide (4.15 9-, 0.0187 mole) and 1 5 ml. of pyridine was heated at reflux temperature for 3 hours and the pyridine was then evaporated. The residue was dissolved in 150 ml. of methylene chloride and 100 ml. of 5$ aqueous hydrochloric acid. The organic layer was separated and washed with water and with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. Crystal lization of the residue from methanol gave a first crop of 4.08 g. of _ [3_ (d imethy lam i no) propy 1 ] -5 , 10-d i hy-d ro-llH-d i benzo[b ,e] [ l,4]d i azep i n-11- th i one melting at 18I-182° C. and a second crop of 0.257 g. melting at 179"l80° C. ; yield 85^.

Anal . calcd. for Ci8H2i 3S: C, 69. 1; H, 6.80; N, 1 . 9; S, 10.30.

Found: C, 69.6l ; H,.6.63; N, 13-l8; S, 10.33.

Example 10 9- [3- (d imethy lami no)propy 1 ] -2,9-di hydro-3H-d ibenzo[b, f]-s-tr?azolo[4,3-d][l,4]diazepin-3-one A mixture of 5' [3~ (d i methy 1 ami no) propy 1 ]d i benzo[b, e ] - [1, 4]d i azep i n-ll-th i one . (0.5 9-, 1.6 mmoles) and ethyl carbazate (1.66 g., l6 mmoles) was immersed in an oi l bath at 192° for 10 minutes, removed and allowed to stand at room temperature for about 72 hours. Water and aqueous layer was separated and extracted five times with 10 ml . portions of methylene chloride. The extract was washed thrice with water and once with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. The residue was triturated with acetone and then crystal lized from acetone to give 0.225 g. of 9"[5~ (dimethy lamiriojpropy 1 ] -2 , 9-d i hyd ro-3H-d i benzofb, f ] -s - t r ΐ - azolo[4,3-d] [l^Jdiazepin-^-one as prisms melting at 212-214° C. After rec rysta 1 li zat i on the product melted at 213-214° C.

Ana 1. calcd. for Ci 9H2 i N50 : C, 68.04; H, 6.31; , 20.88.

Found: C, 67.95; H, 6.3 ; N, 20.64.

Example 1? 6 , 12 -d i ch 1 oro-2 , 9-d i hydro~3H-d i benzo[c, fj-s- triazolo[4,3-a]azepin-3-one In the manner given in Example 1, 3,8-d i ch loro-6 (5H ) morphanthr id i net i one and ethyl carbazate gi e 6,12-di- ch loro-2, 9-d i thiydro-3H-d ibenzof c, f ] - s- tr iazolo[4,,3-a ]aze- p i n-3~one Example ?2. 6 , 12 -d i ch loro-2-ethy 1 -2 , 9-d i hyd ro-3H-d i benzo- [c,f]-s-triazolo[4,3~a]azepin-3"one In the manner given in Example 2, 6, 12-d i ch 1 or o-2 , 9- dihydro-3H-diberizo[c>f]--s-triazolo[4,3_a]azepi n-3~one when treated with sodium hydride and then with ethyl iodide gives 6J12-dichloro-2-ethyl-2J9-dihydro-3H-dibenzo[f]-s- triazolo[4,3"a]azepi n-3_one.

Example τ3 · 12 -ch loro- ,9~d i hyd ro-3H-d ibenzofc, f]-s-tri -azolo[4,3-a]azepin-3-one In the manner given in Example 1, 8-ch 1 oro-6 (5H ) -morphanthr idi ne and ethyl carbazate give 12-cli loro-2 ,9-d ihydro-3H-d i enzo[c, f] -s - t r i azol o[ 4, -a J a ep i n-3-one . ethyl]- 3H-di be nzo[c,f]-s-triazolo[4,3-a]azepin-3_one In the manner given in Example 2, 12 - ch 1 oro-2 , 9- dihydro-3H-dibenzo[c,f]-s-triazolo[4,3~a]azepin-3_one when treated with sodium hydride and then with l-(2-chloro ethy 1 )pyrrol id i ne gives 12 - ch 1 or o-2 , 9-d i hyd ro-2 - [2 - (l- pyrrolidinyl)ethyl]-3H-dibenzo[c,f]-s-triazolo[4,3~a]aze- pin-3~one.

Example 15 6, 12 -d i ch 1 o ro-2 , 9-d i hyd ro-3H- d i benzo[ c, ] -s- tr iazolo[4,3"d] [1, 4]d iazepi n-3- n e In the manner given in Example 5, 2 , 8-d i ch 1 or 0-5 , 10- d i hyd r o-ll-d i benzo[b , e] [ 1 , 4]d i azep?i n- 11- th i one and ethyl carbazate give 6, 12-d i ch 1 oro-2 , 9-d i hyd ro~3H-d i benzo[b , f ] - s-triazolo[4,3-d][l,4]diazepin-3_one.

Example 16 6, 12-D i ch loro-11- [5- (d i methy 1 ami no ) ropy 1 ] -2,9-di hydro-3H-dibenzo[b, f] -s-tr i azolo[4,3"d ] [ 1 ,3] d i azep i n -3_ one In the maner given in Example 5, 2 , 8-d i ch 1 oro- 3- [ 3_ (d i methy lam i no) propy 1 ] -5 , 10 -d i hyd ro-ll-d i benzole] [1,4]-d iazep i n- 11- th i one and ethyl carbazate give 6 , 12- d i ch 1 oro-11- [3- (d i methy lam i no) propy 1 ] -2 ,9-d i hyd ro-3H-d i benzo [b , ] -s-triazolo[4,3"d] [1,4] -d i azep In -3" one .

Example ,1 6,l2-Dichloro-2-[3_ (diethy lami no)p ropy 1 ] -13 -[3- (dimethylamino)propyl]-2,9-dihydro-3H-dibenzo[b, f ] - s -triazolo[4,3-d][l,4]di azep i n~3- one In the manner given in Example 6, , 12 -d i ch 1 or o- 11 -[3-(dimethylamino)propyl]-2,9-dihydro-3H-dibenzo[b,f]-s-tr iazolo[4,3-d] [l,4]d iazepin-3-one was treated with sodium hydride and subsequently with 3~ (d iethylamino)pro-pyl chloride to give 6 , 12 -d i ch 1 oro-2- [3- (d i et hy 1 am i no) -propy l]-ll-[3-(dimethylamiho)propyl]-2,9-dihydro-3H-diben-zo[b,f]-s-triazolo[4,3-d] [ 1 , 4] d i azep i n-3-one .

Example 18 2 - [2 - (d i methy 1 amino)ethyl ] -2,9"dihydro-3H-di - 2932 A J 3H-d i benzofc, f ] -s- t ri azolo[4,3_a]azepi ne-3-one (1.2 g. ) In ether was treated with ethereal hydrogen chloride. Crystal l ization of the thus obtained salt from ethanol -ether gave 1.1 g. of 2- [2- (dimethy lamino)ethy 1 ] -2,9-di hydro-3H-d i benzo[ c , f ] -s - t r i azo lo[4, 3_a Jazep i n-3-one hydrochloride of melting point was 252-253.5° C.

Ana 1. calcd. for Ci 9Η20Ν4Ο· HC 1 : C, 65.95; H, 5.94; N, 15-70; CI, 9-93.

Found : C, 63.90; H, 5-98; N, 15-92.

Example 2, 9-0 ihydro-9-methy 1 -3H-d ibenzo[b, f ] -s- 1 r 1 -azolo[4,3~d] [l,4]d iazepi n-3-one A mixture of 5,10-di hydro-5-methy 1 -llH-d ibenzofb^e] - [1, ]d iazepi n-ll-one (l g., 4.16 mmole) and ethyl car-bazate (4.31 g- ; .16 mmole) was immersed for 30 minutes at 221-225° C. in an oi l bath and the product was processed as described in Example 1. Crystal l ization from methanol gave 0.85 g. of 2 , 9-d i hyd ro-9-methy 1 -3H-d i benzo [b , f ] -s- t r i azolo[4,3-d] [1, 4]d i azepi n-3-one of melting point 159° C.

Ana 1. calcd. for Ci5Hi2N40: C, 68.17; H, 4.58; N, 21.20 Found: C, 67-95; H, 4.66.

Example ¾ 2- [2- (D i methy 1 ami no) ethy 1 ] -2 , 9-d i hyd ro- 9-methy 1 -^H-di benzo [b, f ] -s-tr iazolo[4J3-d] [l,4]diazepi n-3-one and its hydrochloride Sodium hydride (0.169 g., 4 mmoles of a 57$ dispersion in mineral oi l) was added to a solution of 2,9-dihy-dro-9-methy 1 -3H-dibenzo[b, ]-s-tr i azolo[4,3"d] [l,4]diaze-pin-3-one (1.09 g., 4 mmoles) in 35 ml . of dimethylfor- The mixture was then cooled to about 40 C. A solution of 2-d imethy laminoethy 1 chloride (0.428 g., 4 mmoles in 0.428 g. of xylene) was added and heating at 95° C. was continued for l8 hours and then evaporated to dryness in vacuo to give 2 - [2- (d imethy 1 ami no) ethy 1 ] -2 ,9-d i hyd ro- 9-methy 1 -5H-d i benzo[b, f]-s-triazolo[4,3-d][l,4]diazep i n-3~one . Ether and water were added to the thus obtained residue. The organic layer was extracted three times with 10 ml. portions of 10$ aqueous sodium hydroxide and the base mixture extracted with methylene chloride. The extract was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and evaporated to dryness. The hydrochloride of the base was prepared in ether with ethereal hydrogen chloride and was crystall ized from methanol ether to give 0.518 g. of 2- [ - (d i methy 1 ami no)ethy 1 J -2 , 9-dihydro-9-methy 1 -3H-dibenzo[b, f ] -s-tr iazolo[4,3-d] [1,4] -diazepin-^-one hydrochloride of melting point 293-29 ° C. Ana 1. calcd. for Ci9H2iN50-HCl : C, 61.36; H, 5.96; CI, 9-53; N , 18.84.

Found: C, 6l.20; H, 5.93; CI, 9-52; N, l8.30.

Example j¾ 7- Ch 1 oro- , 9-d i hyd ro~3H-d ibenzo[c, f ] -s- 1 r i azo-lo[4,3-a]azepin-3~one A mixture of 2-ch loro-6 (5H ) -morphanth r i d inethione (2.6 g., 0.01 mole) and ethyl carbazate (10.4 g., 0.1 mole) was immersed for 50 minutes at 220-227° C. in an oi l bath which had been preheated to that temperature. During this time 4 ml. of l iquid was col lected via a takeoff condenser.

The product was a glassy solid which was ground, and to it water and chloroform were added. The mixture was ex- solution, dried over anhydrous magnesium sulfate and evaporated to dryness. Crystal lization from methanol of the residue gave a first crop of 1.2 g. of 7~ch 1 oro-2 , 9-d i hy-dro-3H-dibenzo[c, f ]-s-triazolo[4,3-a]azepin-3-one in pale yel low needles which melted at 272-2730 C. (unchanged on recrysta 11 i zat i on ) . A second crop of product weighed 0.45 g. and melted at 267-269° C ; yield, 59$ Ana 1. calcd. for Ci5HiOClN30: C, 63.50; H, 3.55; Cl, 12.50; N, 14.8l.

Found: C, 62.99; H, 3.49; Cl, 12.42; N, 14.78. 22 Exam le ffl 2 , 9-D i h d r'o-2- [2- (l -me thy 1 -2-py r ro 1 i d i ny 1 ) -ethy 1 ] -3H-d i benzo[c, f ] -s - 1 r i azo 1 o[ , 3-a]azepi n-3-one In the manner given in Example 2, 2 , 9-d i hyd ro-3H-d i benzo[ c, f ] -s - t r i azo io[4,3_a ]azep i n-3-one was treated with sodium hydride and thereafter with 2- (l-methy 1 -2-pyrrol id i ny 1 )ethyl chloride to give 2 , 9-d i hydro-2 - [2 - (l-methyl-2-pyrrol idinyl )ethyl]-3H-dibenzo[c,f]-s-triazolo-[4,3-a]azepin- -one .

Example ¾ 7" Ch 1 oro-2- [2- (d i nethy lami no) ethy 1 ] -2 , 9-d i hy-d ro~3H-d ibenzo[c,f]-s-triazolo[4,3-a]azepi n-3_one Sodium hydride (O.I88 g., 4.47 mmoles of a 57$ dispersion in mineral oil ) was added to a solution of 7~chloro-2,9-di hydro~3H-d ibenzo[c, f ] -s - 1 r i azo 1 o[ 4, 3-a ] azep i ne-3-one (I.25 g 4.47 mmoles) in 0 ml. of d imethyl formamide and the mixture was heated at 95° C. for 25 minutes. The mixture was cooled, a solution of 2-d imethy 1 am Ϊ noethy 1 chloride (0.48 g., 4.47 mmole) in 0.48 g. of xylene was added and the mixture was cont i nua 11 y heated at 95° C. for 16.5 hours. The product was isolated according to the 2932A^, Ο.92 g. of 7-chloro-2-[2- (dimethylamino)ethyl]-2i9-dihy-dro-3H-dibenzo[c, f]-s-triazolo[4,3_a]azepi n-3_one me 11 i ng at 152-153° C. (unchanged on recrysta 11 izat ion) .

Ana 1. calcd. for Ci9Hi9ClN40: C, 64.31; H, 5.4l0; CI , 9-99; N, 15-79.

Found : C, 64.17; H, 5-49; CI, 9-99; N, 15.57- 24 Example ffl Dibenzo[b, f ] - s-tr i azol o[ 4,3"d ] [l,4]oxazepi n- >- (2H)-one A mixture of d i benzo[b , f ] [ 1 , ] oxazep i n-11 (lOH ) - th i one (2.59 g., 0.01 mole) and ethyl carbazate (10.4 g. , 0.1 mole) was immersed for 15 minutes at 205"210° C. in an oi l bath which had been preheated to that temperature.

During that time 1 ml . of l iquid was col lected via a take-off condenser. The clear yel low solution was cooled to about 40° C. and di luted with 50 ml . of water. The resulting suspension was fi ltered and the d ibenzo[b, f ] -s-t r i azo lo[4,3_d] [ 1, 4] oxazep i n-3 (2H) -one thus obtained was washed with water and crystal l ized from methanol, weight 1.6 g. melting point 258-260° C. Second crop weighed 0.248 g. and melted at 253-2 5° C.

Ana 1. calcd. for C14H9N3O2 : C, 66.93; H, 5.6l; N, 16.73.

Found: C, 66.70; H, 3-53; N, 16.85.

Example 49 2- [2- (D i met hy 1 am i no ) eth 1 ] d i benzo [ b , f ] - s - 1 r i -azolo[4,3"d] [l,4]oxazepin-3(2H)-one Sodium hydride (0.218 g., 5-17 mmoles of 57$ suspension in mineral oi l ) was added to a solution of dibenzo-[b,f]-s-triazolo[4,3"d] [l,4]oxazepin-3(2H)-one (1.3 g., 5.17 mmoles) in 0 ml . of d imethy 1 formamide and the mix- - 2-d imethy lami noethy 1 chloride (0.555 g · 5.17 mmoles) in 0.555 g. of xylene was added and the mixture heated at 95° C. for 1 hours. The product was isolated according to the procedure of Example 2. The product thus -obta i ned was crystal l ized from ether and petroleum ether (b . p . 30-60°) to give 0.65 g. of 2- [2- (d imeth lam i no)ethy 1 ]d i benzo[b , f J -s-triazolo[ ,3-d] [l, ]oxazepin-3(2H)-one melting at 109-111° C. After recrysta 11 i zat i on from ether the melting point was 103-104° C.

Example ¾ 2 , 9- 0 i hyd ro-2- [3- (l-p i per i d i ny 1 ) propy 1 ] -3H-dibenzo[c, ] - s- 1 r i azol o[ 4, 3" a ] aze i n-3- one I n the manner given in Example 2, 2 , 9-d i hyd ro-3H-d i benzo[c, f ] -s- t r i azolo[4, 3~a ]azepi ne-3-one was treated with sodium hydride and the resulting product was treated with 1- (3-ch 1 oropropy 1 )p i pe r i d i ne to give 2 , < -ά i hyd ro-2 - [3" (l-piperidinyl )propy 1 ] -3H-d ibenzo[c, f ] -s- 1 r iazolo[4,3-a ] -azep i n-3-one . 27 Example *2 2 , 9-0 i hyd ro-2 - [2- (l-methy 1 -2- py r rol idinyl)-propy 1 ] ~3H-d i benzo[c, f]-s-triazolo[4,3_a]azepi n-3- one Two grams (0.00805 mole) of 2, 9-d i hyd ro-3H-d ibenzo- [c, f] -s- triazolo[4,3_a]azepi n-3-one was treated with 194 mg . of sodium hydride in d imethy 1 formamide and thereupon with 1.18 g. of 2- (3_ch loropropy 1 ) -l-methy 1 pyr rol idine to give 1.7 g. of 2 , 9-d i hydro-2 - [2- (l-Methy 1 -2- py r ro 1 i d i ny 1 ) -propyl ]-3H-dibenzo[c, f]-s-triazolo[4,3-a]azepin-3-one as an amorphous sol id.

Example ¾ 2- [2- (Diethylamino)ethyl]-2i9-dihydro-3H-d ibenzofc^ f ] -s - t r i azol o[4 j3"a]azepi n-3-one and maleate the reof dibenzo[c,f]-s-triazolo[4,3-a]azepin-3-one was treated with sodium hydride and then with d i ethy 1 am i noethy 1 chloride gave 2- [2- (d i ethy lami no)ethy 1 ] -2 , 9~d i hyd ro ~3H-d i benzo-[c, f ] -s-tr iazolo[ i3_a]azepin-3_one as a yel low oi l .

This product was converted with maleic acid in ether to 2- [2- (d i eth lami no) ethyl] -2, 9-dihydro-3H-dibenzo[c, f ] -s-tr iazolo[4,3~a]azepi n-3-one maleate of melting point, 147-148° C.

Ana 1. calcd. for C21 Η24Ν40· C4H404 : C, 64.64; H, 6.Ο8; N, I2.O6.

Found; C, 64.58; H, 6.01; N, 12.10.

Example % 2,9-Di hydro-2- [2- (l-p i per i d i ny 1 )ethy 1 ] -3H-d ibenzo[c, f ] -s - 1 r i azol o[4,3-a]azepi n-3-one hydroch 1 or i de In the manner given in Example 1, 2 , 9-d i hyd ro~3H-d i benzo[c, f ] - s- t r i azolo[4 j3-a ]azep i n-3-one was treated with sodium hydride and l- (2-ch loroeth 1 )pi per id i ne to give after extraction with hydrochloric acid 2,9-dihydro-2-[2-(l-piperidinyl)ethyl] -3H-d i benzofc, f ] -s- 1 r iazolo-[4,3_a]azepi n-3-one hydrochloride of melting point 246.5" 248° C.

Exam le 4¾ 2,9-Dihyd ro-2- [2- (methy 1 am i no) ethy 1 ] -3H-dibenzo[c,f]-s-triazolo[4i3_a]azepin-3"one A solution of 2,9~dihydro-2- [2- (d imethy lamino)ethy 1 ] - 3H-d i benzo[c, f ] -s- t r iazol o[4,3"a] azep i n-3-one in benzene and chloroform was heated with ethyl ch 1 oro formate at reflux temperature for 12 hours to give 2- [2- [ (ethoxyca r-bony 1 )methy lami no] ethy 1 ] -2 , 9-d i hyd ro-3H-d i benzol f ] - s-tr iazolo[4,3_a]azepi n-3-one .

This product in propylene glycol containing potassium give 2-[2- (methy lam i no) ethyl ] -2, 9"dihydro-3H-di benzo[c, f ] - s-t ri azol o[4,3-a]azepi n-3-one of melting point 125-126° C.

The hydrochloride of 2 , 9~d i hydro-2- [2- (methy lam i no ) - ethyl ]-3H-dibenzo[c, f ] - s - 1 r i azo 1 o[ , 3" a ] azep i ne-3"one was prepared by mixing the base with anhydrous hydrogen chloride in ether, melting point 257-259° C.

Example 31 2- [ ( 1-methy 1 p i per i d i ny- - y 1 )meth y 1 ] -2 , 9"d ' hY " dro-3H-dibenzo[c,b]-s-triazolo[4i3_a]azepin-3"one hydro-ch 1 or i de In the manner given in Exampfe 2, 2 , 9-d i hyd ro-' H-d i benzo[ c, b ] - s - t r i azol o[ 4 , 3~a ] azep i n-3-one , sodium hydride and 1 -methy 1 - -ch loromethy 1 p i per i d i ne gave after extraction with hydrochloric acid 2 - [ (l -methy 1 p i e r i d i ny 1 -2- y 1 ) -methyl J-2,9-dihydro-3H-dibenzo cib]-s-triazolo[,4,3-a]-azepin-3_one hydrochloride of melting point 150-151° C. Example 32 7- Ch 1 oro-2- [2- (d i met h y 1 am i no ) eth y 1 ~3H-d i benzo-[b, f] -s-tr iazolo[4,3-d] [ 1, ] oxazep i n-3- (2H)-one I n the manner given in Example 2, 7-ch loro-d ibenzo-("b, f j-s-triazolo[ ,3-dJ [ 1 , 4 ] oxazep i n -3- (2H)-one, sodium hydride and (d i methy 1 ami no)ethy 1 chloride gave 7-chloro-2- [2- (dimethylamino)ethylJdibenzo[b, f]-s-triazolo[4,3-d] -[ 1 „ 4] oxazepi n-3" (2H ) -one of melting point 142-143° C.

Example 3¾ D i benzo [ b , f ] - s - t r i azo 1 o[ 4 , 3-d ] [ 1 , 4] th i azep i n- 2952 A (2H)-one In the manner given in Example 1, d i benzo[b , f ] [ 1 , 4] -th iazep i n- 11 (lOH ) - th ione and ethyl carbazate were reacted to give d i benzo[b , f ] -s - 1 r i azol o[4, 3"d ] [ 1, 4] th i aze i n-3 (2H ) -one melting at 302-303°. 34 Example ¾Q 2- [2- (D imethy 1 ami no ) ethy 1 ]d i benzo[b , f] - s - 1 r i -azolo[4,3-d] [1,4] th iazep i n-3 (2H) -one hydrochloride In the manner given in Example , d i benzo[b, f ] -s-tr iazolo[4i5"d] [ 1 4] th i azep i n-3 (2H ) -one was first treated with sodium hydride, and the resulting product with (dimethyl ami no)ethyl chloride to give after extraction with hydrochloric acid 2 - [2- (d imethy 1 ami no)ethy 1 ]d i benzo[b, f ] -s-triazolo[4,5-d] [ 1 ,4 ] th i azep i n- (2H ) -one hydrochloride of melting point 292-2930 c.

Example 6- Ch 1 oro-2- [2- (d imethy 1 ami no)ethy 1 ]d i benzo- [b, f] -s-tri azol o[4,5"d] [1,4] oxazep in-5(2H)-one In the manner given in Example 2, 6-ch 1 oro-d i benzo-[b, f ] -s-tr iazolo[4,5-d] [ 1, 4] oxazep i n- (2H ) - one, sodium hydride and 2- (dimethylamino)ethy 1 chloride gave 6-chloro-2- [2- (d i methyl ami n o) ethy 1 ]dibenzo[b, f] -s-tr i azol o[ , 3-d]-[1, 4] oxazep i n-3 (2H) -one .

Exampl e j γ-Ch 1 oro-2- [2- (d imethy lam ino)e thy 1 ] -2, 9-di'hy-d ro~3H-d ibenzo[c, f ] -s- 1 r i azol o[ 4,5" d] [ 1,4] d i azep i ne-5-one hyd roch 1 or i de In the manner given in Example 4, 7-ch 1 oro-2 , 9-d i hydro- 3H-dibenzo[c,f] -s-tr iazolo[4,3"d]di azepi n-3- one, prepared as in Example 2 from 7~ch loro-5, 10-d i hydro-llH-dibenzo[b,e] [ 1, 4] d iazep i n-11- th i one and having a melting point fo 289 to 2900 C, and 2- (d imethy lami no)ethy 1 chlor- 2932 A 2- [2- (dimethyl ami no) ethyl -2 , 9-d i hydro-3H-d i benzo[c, f]-s- t r i azol o[ ,3-a ] [ 1 , 4]d i aze i n-3_one hydrochloride of melting point 263- 6 ° C. 37 Exam le 5-5- 2- [3- (phthal imido)ethyl ] -2 , 9-d i hyd ro~3H-d i ben-zo[c,f] -s- 1 r iazo lo[4,3-a Jazep i ne-3-one Sodium hydride (0.421 g. ; 0.01 mole of 7$ dispersion in mineral oi l ) was added to a solution of 2,9-dihydro-3H-d i benzo[c, f ] - s- t r i azol o[4,3-a Jaze i ne-3-one (2.49 g. ; 0.01 mole) in 50 ml . of d imethy 1 formamide and the mixture was heated for 40 minutes at 95° C. A solution of N- (2-bromoethy 1 )phtha 1 imide (2.54 g. ; 0.01 mole) in 15 ml . of dimethyl formamide was then added during 2 minutes and the mixture was heated at 95° C. for 17 hours. It was evaporated, 0 ml . of water was added and the resulting sus-pension was fi ltered. The sol id was crystal l ized from methanol to give 2.8 g. of 2- [3- (phtha 1 imido)ethy 1 ] -2,9-dihydro-3H-dibenzo[c,f]-s-triazolo[ i3~a]azepi ne~3-one of melting point l84-l85° C. raised to 186-187° on recrys-ta 11 i zat i on .

Ana 1. calcd. for C25Hi8 403 : C, 7I.O8; H, 4.29; N, 13.26.

Found: C, 71.10; H, 4.29; N, 13-13. 38 Example -54 2 -[2- (ami no)ethy 1 ] -2 , 9-d i hyd ro-3H-d i benzo[c, f ] -s -tr i azolo[ ,3"a]azepi ne-3-one and its napsylate acid addition salt A mixture of 2- [3- (phthal imido)ethyl ] -2 , 9-d i hyd ro-3H-dibenzotc, f] -s-tr iazolo[4,3-a]azepine-3-one (1.89 g. ; 4.47 mmole), hydrazine hydrate (9.0 g. ; 0.0179 mole) and 25 ml . of ethanol was stirred at room temperature for 24 hours . 2932 A The fi ltrate was evaporated, the resulting res idue was dissolved in methylene ch loride-water. The extract was washed with water dried over anhydrous magnesium sulfate and evaporated to give 0.6 9 g- of 2- [-$- (ami no)ethy 1 ] 2,9-dihydro-3H-dibenzo[c, f]-s-triazolo[ ,3_a]azepi ne-3-one The napsylate salt (β-naphtha 1 ene sulfonic acid addition salt ) was prepared in methanol and recrys ta 1 1 i zed from methanol , melting point 28l.5~283°. 39 M .

Example 2- [2- [ (JM-bcnsy l- -rrfethy 1 am i no) ethy 1 ]-2,9-d i hyd ro-JH-d ibenzo[c,f]-s-triazolo[ ,3~a]azepi ne-3- one hyd roch 1 or i de I n the manner given in Example 2, 2 , 9-d i hyd ro-3H-d i benzo[c, f ] -s -t r i azolo[ ] azep i ne-3-one, when treated with sodium hydride and then with 2- (benzy lmethy lami no) ethyl ch loride gave 2- [2 - ( N-benzy 1 - N-methy lami no)ethy 1 ] - 2 , 9-d i hyd ro-3H-d ibenzo[c, f]-s-triazolo[1l-,3-a]azepine-3-one of melting point 9δ-99·5° C. Hyd rogenat i on of this compound by the usual procedure gave the compound of Example 45, 2 , 9- di hydro-2- [2 - (methy 1 am ino)ethyl ]-3H-diben-zo[c, f] -s-triazolo[ ,3~a]azepi n~3-one . 40 Exam le - 6- 6- Ch 1 oro-2 , 9-d i hyd ro-3H-d i benzo[ c, f ] -s-tr i -azolo[ ,3-a]azepin-3_one A mixture of J>-c 1 oro-6- (5H ) -mor phanth r i d i neth i one (26.5 9-, O.IO3 mole) and ethy 1 ca rbazate (l07 g. , 1.03 mole) was immersed for 120 minutes at 210-215° C. i n an oi l bath which had been preheated to that temperature.

During this time ½5 ml . of l iquid was col lected via a take-off condenser. The product was a sol id which was ground, and to it water and chloroform were added. The 2932 A extracts were combined, washed with water, and saturated salt solution, dried over anhydrous magnesium sulfate and evaporated to dryness to crystal lization from methanol-chloroform of the residue gave 9.5 g. of 6-ch 1 oro-2 9-dihydro-3H-dibenzo[c, f]-s~triazolo[4,3_a]azepi n-J-one which melted at 266-267° C. (unchanged on recrysta 11 iza-tion). The second crop was 3.65 g. of melting point 265-266° C.

Ana 1. calcd. for Ci5HiOClN30: C, 63.50; H, 3-55; CI, 12.50; N, l4.8l.

Found: C, 63.43; H, 3-70; CI, 12.80; N, 14.79-Example ' 6-Ch loro-2- [2- (d i methy 1 am i no)ethy 1 ] -2,9-di hydro ~3H-dibenzo[c, f]-s-triazolo[4,3~a]azepi n-3-one Sodium hydride (0.97 g., 3 mmoles of a 57^ d i s -persion in mineral oi l) was added to a solution of 6-chloro-2,9-dihydro-3H-dibenzo[c,f]-s-triazolo[ ,3-a]aze-pine-3-one (6.5 g 23 mmoles) in 230 ml . of dimethylfor-mamide and the mixture was heated at 95° C. for 40 minutes. After reacting with d i methy lam i noethy 1 chloride the product was isolated according to the procedure of Example 2. Crystal lization from ether gave 6-chloro-2-[2-(dimethylamino)ethyl]-2,9-dihydro-3H-dibenzo[c,f]-s-tr iazolo[4,3_a]azepi ne-3-one of melting point 158.5-160° C.

Ana 1. calcd. for Ci9Hi9ClN40: C, 64.31; H, 5.40; CI, 9-99; N, 15.79- Found: C, 64.39; H, 5.40; CI, 9-85; N, 16.20. 42 Example ¾& 7-Ch loro-d ibenzo[b, f]-s-triazolo[4,3-d]-[ 1, 4]oxazep i n-3 (2H)-one 41277/2 - ' zo[b, f] [l,4]oxazepin-ll(lOH)-thione and ethyl carbazate were reacted to give 7-ch loro-d i benzo[b , f j -s-triazolo- [4, 3-d] [l,4]oxazepin-5(2H)-one of melting point 313"3 i- Example ,43 7- Ch loro-2 - [3 " (d i methy lam i no ) p ropy 1 ] d i ben :o [b,f]-s-triazolo[Jri3-d] [lJ4]oxazepin-3(2H)-one and it , hyd roch 1 or i de I n the manner given in Example25 , 7-ch loro-d i b n zo[b, f ] - s-tr iazolo[ ,3"d] [1,4] ox izepi n-3 ('?H)-one was treated with sodium hydride and .hen with 3-d i meth l- aminopropyl chloride to give J- ch 1 o ro-2 - [ ~ (d i meth y 1 a n i propyl ] -d i benzo[b , f ] -s - 1 r i azo 1 o[ , 3-d ] [ 1 , 4 ] oxazep i n-3 (2 one hydrochloride of melting point 228-229° C. " " Example 44 2- \ >- (dimethyl ,) ami nop ropy 1 ] d ibenzo[b, f ] -s - triazolo[ ,3-d] [l,4]oxazepin-3(2H)-one- and its hyd roc i l ide I n the m.jnner given in Example 25., d i benzo[b , f J - ; -, t r i azo 1 o[4 , 3-d "j [ 1, 4 ] oxazep i n-3 (2H ) -one was first trea.e with sodium hydride and the resulting product with 3" d imethy 1 am i nopropy 1 chloride to give after extraction w hydrochloric acid, 2- [3- (d imethy 1 )ami no d fbenzo[b, f ] - 5 - t r i azol o[ , -d ] [ 1 , ] oxazepi n-3 (2H )-one hydrochloride )f molting point l83-l34° C. as a partial hydrate.

Example ,45 7- Ch 1 o ro-d i benzo[ b , f J - s - 1 r i azol o[ 4, 3-d ] [1 , th i azep i n~3 (211 ) -one ' . I n" the manner given in Example 1, 7-ch 1 oro-d i be iz [b,f ] [l,4]thiazepi n-11- (lOH)-thione and ethyl carbazaie were reacted to give 7-ch 1 oro-d i benzo[b, ] -s - t r i azol o - [4,3-d] [l,4]thiazepi -3(2H)-one of melting point 293- >9 Exam le 46 7- Ch 1 oro-2- [2 - (d i met hy 1 ami no) ethy 1 ] -d iben :ο [b,f]-s-triazolo[4,3-d] [l,4]thia'epin-3(2H)-one ■■ In the manner given in Example 4 , J-ch loro-d i benzo- [b, f ]-s-triazolo[4,3"d] [ 1 , 4] t h i aze i n-3 (2H ) - one was first reacted with sodium hydride, and the resulting product with 2 - (d i methy 1 ami no)ethy 1 chloride to gi e 7-chloro-2- [ 2- (d imethy 1 ami nolethy 1 ]dibenzo[b, f ] - s - t r i azo 1 o [ 4 , 3" d ] [1,4] th iazep i n-3 (2H ) -one of melting point 121-122° C. 47 Example * 7-th loro-2- [3- (d imethy lami no)propy 1 ] -d i benzo- [b,f j-s-tr iazolo[4,3-d] [l,4]thiazepi n-3(2H)-one In the manner given in Example 4, 7-ch 1 oro-d i benzo- [b, f] -s-tr iazolo[4,3-d] [ 1 , ] th i azep i n -3 (2H ) - one was first reacted with sodium hydride and the resulting product with 3- (dimethy 1 am i no ) ropy 1 chloride to give 7- ch 1 or o-2 - [ - (d i methyl am ino) ropy 1 ]dibenzo[b,f)-s-triazolo 4,3-d][l,4]~ thiazepin-3(2H)-one of melting point 123-125° C.

Example £Q 2 , 9-D i hydr 0-9, 9~d i methy 1 -3H-d i benzo[ c , f]-s-triazolo[4,3-a]azepin-3"one 2932 A A. 6-Chloro-ll,ll-dimethylmorphanthridine A melt of 11, 11-d imethy 1 -6 (5H)morphanthr id i none (4.72 g. ; 0.02 mole) with phosphorus pentach 1 or ί de (5-8 g „ ; 0.028 mole) was sti rred under nitrogen at 130° C, for 2 hours. The P0C13 which had formed was disti l led off under reduced pressure leaving a red viscous oi l (5.1 g.). This was crystal lized and used in the next preparation without further purification.

B. 11,11-Dimethylmorphanthridi ne- N-ca rbethoxyhyd raz i de 6- Ch 1 oro-11 , 11-d i methy Imor phanth r i d i ne (5.1 g. ; 0.02 mole) prepared as above and ethyl carbazate (10.4 g. ; 0.1 mole) in 200 ml. of absolute ethanol was refluxed under nitrogen for 21 hours and then evaporated to dryness in vacuo. The residue was dissolved in 100 ml. of methyl-ene chloride and washed with 2$ cold NaOH then with water and evaporated in vacuo to give 6.1 g. of 11, 11-d imethy 1 -mor phanth r i d i ne-N-ca rbet hoxy-hyd raz i de which was used in the next step without further purification.

C. 2,9-Di hydro-9,9-dimethy l-3H-dibenzo[c, f]-s-triazolo-[4,3_a]azepi n-3_one 11, 11-0 imethy 1 mor phanthr id i ne-N-carbethoxyhydraz ide (6.4 g. ; 0.02 mole) prepared above in 100 ml. of n-butanol was refluxed under N≥ for 24 hrs. The solvent was evaporated in vacuo to leave an oi l which was dissolved in 40 ml. of CHCI3, washed with cold 5$ NaOH, H20, and concentrated to a viscous, colorless syrup. This was crystal lized using acetone to give 1.53 g. of 2 ,9-d i hyd ro-9, 9-dimethyl-3H-dibenzo[c,f]-s-triazolo[4,3-a]azepin-3-one as white needles, melting point 311-314° C. 2932 A C, 73·β3; H, 5.45; N, 15.15.

Found: c, 73-14; H , 5-43; N, 14.89. 49 Example 6/1 2, 9-D i hyd ro-2- [2- (d i methy 1 am i no )ethy 1 ] -9, 9-d i methy 1 -3H-d i benzo[c, f ] -s- 1 r i azol o[ 4 ,3" a Jazepi n-3- one A mixture of 2 , 9-d i hyd ro- 9, 9-d imethy 1 ~3H-d i benzofc, f ] -s-triazolo[ ,3-a]azepin-3_one (I.38 g. ; 0.005 mole) and sodium hydride in mineral oi l ( 0$, 250 mg. ; 0.006 mole) in 0 ml. of OMF was heated under N≥ at 95° for 40 minutes. To this was added d imethy lam i noethy 1 chloride (0.01 mole) in benzene and stirring and heating were continued for 7 hours. The DMF was removed in vacuo to give a syrup which was dissolved in 0 ml. of CH2C12 and water. The organic layer was extracted with cold 10$ HC1 and the acid solution was basified and extracted with CH2CI2.

Evaporation of the solvent gave a residue which was crystal lized from CH2C12. Skellysolve B to give 6.50 mg. of 2,9-di hyd ro-2- [2- (d i methy 1 ami no) ethy 1 ] - 9, 9-d i methy 1 -3H -d i benzo[ Cj f ] -s- tr i azol o[ ,3~a ]azep Ϊ n-3-one of melting point 148-149°.

Anal, calcd. for C21H24N4O: C, 72.38; H, 6.94; N, l6.08.

Found: C, 72.42; H, 6.97; N, 16.38. 50 Exam le 68 6 - Ch'loro-2- [3 - (d imethy lam i no) p ropy 1 ] -2 ,9-dlhydro-3H dibenzo[c, f] -s-tr iazolo[4,3-a]azepin-3_one and its oxalate In the manner given in Example 2, 6- ch 1 oro-2 , 9-d i hy-dro~3H-d ibenzo[c, f ]-s-triazolo[4,3-a]azepin-3-one was treated with sodium hydride and thereafter with 3-(dimethylamino)propyl chloride to give 6-ch loro-2- [3- t r i azo 1 o[ 4, 3-a ] azep i n-3~one as an oi l . The oxalate salt was prepared from oxal ic acid in ether and had a melting point of 235-2 6° 51 2,9-Dihydro Examp 1 e ~5¾ /2-'[2- (4-methyl-l-pi eraziny1 )ethyl]-j5H-dibenzo- [c, f ]-s-triazolo[4,3-a]azepin-3_one and its d ihydroch lor ide In the manner given in Example 2, 2 , 9~d i hyd ro-3H-d i benzo[ c , f ] - s- t r i azol o [4, 3-a ] azep i n-3~one was treated with sodium hydride and thereafter with 1- (2-ch loroethy 1 ) - 2,9-Dihydro 4- methy 1 p i peraz i ne to g i ve 2- [2 - ( -met hy 1 - 1- p i peraz i ny 1 ) -ethyl]- 3H-dibenzo[c, f]-s-triazolo| 4,3_a]azepin-3- one as an oi l . The oi l was dissolved in ether and treated with ethereal HCl to give the d i hyd roch 1 or i de as a hydrate, melting point 245°. The anhydrous salt can be obtained by vacuum drying.

In the manner i l lustrated in the preceding examples other thiones of f ormu 1 can be converted with an a 1 ky 1 carbazate such as methyl, ethyl, propyl, or i opropyl ca -bazate to an azepine, diazepine, oxazepine or thiazepine of formula I I . Representative compounds of formula I I , thus obtained, include: 6,l2-dic loro-9,9-dimethyl-2,9-dihydro-3H-dibenzo[c, f ]-s-triazolo[4,3-a]azepin-3~one ; - omino-9>9"d i othy 1 "2 J91 di hyd ro 31l"dibcnno[c, f ] o trioaolo [ Ί ,3-Q.] oaop i n"3none ) 2,9-d i hydro- 9-methy 1 -3H-d i benzo[c, f ] -s-triazolo[4,3-a]aze-pin-3"one; 2, 9- di hydro- 9- propyl -3H-d i benzo[c, f]-s-triazolo[4,3"a]aze-pi n-3"one ; . 12-chloro-2,9-dihydro-3H-dibenzo[b, f] -s-tr iazolo[4,3~d] - [l, ]diazepin-3-one; 6,12-d i ch lor 0-9- (dime thy lam i no )me thy 1 -2,9-d i hyd ro- 3H-dibenzo[b, f ] -s - t r i azo 1 o[4, 3"d ] 1 , ] d i azep i ne-3- 6,12-d i ch loro-d ibenzo[b, f ] - s - t r i azo 1 o[4, 3-d ] [ 1 , 4] oxazep ί n- 3- (2H)-one; 7-ch loro-d ibenzo[b, ] -s-tr i azol o [ 4 3" d ] [ 1 , 4 J oxaze i n -3 (2H ) -one ; 7-ch lor o-dibenzo[b, f ] -s - t r i azo 1 o [ , 3-d ] [ 1 , 4 ] th i azep i n-3(2H)one; 6, 12 -d ich loro-d ibenzo[b, f] -s-tr iazolo[4,3-d] [l,4]thiaze-pin-3(2H)one; and the 1 i ke .

Treating these compounds of formula I I with a strong base e.g. sodium hydride, potassium hydride, sodium butox- ide, potassium isopropoxide fol lowed by a ha 1 ogenated compound of formula R2X wherein R2 is defined as herein above, and X is halogen selected from chlorine, bromine, or iodine gives the corresponding compounds of formula I I I . Representative compounds, thus obtained, include: 6,12-d ich lor 0-2- [3' (d i e thy lam i no ) p ropy 1 ] -9, 9~d i methyl - 2 , 9-d i hyd ro~3H- d i benzo[ c, f] -s-tr iazolo[4,3-a]azepin-3" one; 12-ch loro-2- [2- (d i et h la m i no )eth 1 ] -2 , 9-d i hydro-3H- d i benzo- [b,f]-s-triazolo[4,3_d] [l,4]diazepi 11-3 - one; 6,12-d ich loro-2,9-bis[ (d imethy lami no)methy 1 ] -2 , 9-d i hydro-3H-dibenzo[b,f ]-s-triazolo[4,3-d J [l,4]diazepi n-3-one ; 6,12-d ich loro-2- [3- (d i methy 1 am i no ) p ropy 1 ] d i b enzo[ , f ] - s - tr iazolo[4,3-d] [ 1 , ] oxazep i n-3 {ί' ) one ; 6- ch loro-2- [2- (4-methyl-l-piperazinyl )ethyl ]di benzol b,f]- s-tri azolo[4,3"d] [ 1 ,4 ] oxazep i n-/i (2H )one ; 7- ch loro-2- [4- id i ethv lami no &bu tyrrl - y 1 ]d i benzo[b , f ] -s- t r i - azolo[4,3-d][l ,4]oxazepin-3(2H)one; 7-chloro-2-[3-(di propyl amino)propyl ]di enzo[b,f]-s-triazolo [4,2-d][l ,4]t iazepin-3(2H)one T 7- Ch loro-2- [2- (4-methy 1 -1-pi peraz i n 1 ) eth 1 ] -2 ,9-d i hydro-3H-dibenzo[c, f ] - s - 1 r i azo 1 o[ , 3~a ] azep i n-3-one ; 7- Ch loro-2 -[3- (dimethyl ami no) propyl ] -2 , 9-d i hyd ro-3H-d i ben zo[c, ]-s-triazolo[ ,3-a]azepin-3-one ; 7- Ch loro-9,9-dimethy 1 -2- [2- (d i methy 1 am i no ) ethy 1 ] -2,9-dihy dro-3H-di enzo[c, f ] - s - 1 r iazo lo[4,3_a Jazep i n-3-one ; 6- Ch 1 oro-2- [3- (4-methy 1 -1-pi peraz i ny 1 )propy 1 ] -3H-d i benzo-[c, f ] -s - 1 r i azol o[4,3-a ]azepi n-3-one ; 6-Ch 1 oro-2- [2- (d i methy 1 am i no) ethy 1 ] -9,9-d imethy 1 -3H-d i ben zo[cif]-s-triazolo[ ,3-a]azepin-3-one; 2 -[2- (d imethy ] am ino)eth l] -2, 9-d i hyd ro-3H-d i benzo[b, ]-s -triazolo[ ,3-d] [1 , 4]d i azep i n-3-one ; and the Π ke .

Treatment of the compounds of formula I I and I I I with a pharmacologically acceptable acid such as hydrochloric, hydrobromic, phosphoric, sulfuric, acetic, propionic, toluenesu 1 fon i c, naphtha 1 ene-β- su 1 f on i c, methane-sulfonic, tartaric, citric, lactic, malic, maleic, or eye lohexanesu 1 fami c (acids) produces the pha rmaco 1 g i ca 11 y acceptable salts of these compounds of formula 'I I and I I I The salts can be used for the same purposes as the free base compounds of formula I I and I I I .

Salt formation is achieved in conventional manner by reacting the compounds of formula I I I with an excess of a selected acid in a suitable medium e.g. water, alkanol, ether, or acetone and recovering the salt by evaporating the solvent, preferably in vacuo.

Claims (1)

1. 41277/ 3 WHAT IS CLAIMED IS: A compound selected from the group consisting of triazoloazepi nes of the formula I I I : wherein X is selected from the group consisting of oxygen, in which R5 and Re are each selected from isting of hydrogen and a 1 ky I of 1 to 5 carbon atoms inclusive, ^ - R , in which R , is hydrogen CH3-N, N-CnHsn- ; in which n is 1 to 4, inclusive and R is alkyl defined as above, or is in which R-, and Rg are each selected from the group consisting of hydrogen and alkyl as defined above and n is defined as above, or together -N is pyrrolidino and piperidino; iherein has the same significance as ; or it is (benzylmethylnmino) ethyl, and wherein ^ and are each selected from the group consisting of hydrogen, chloro, and the pharmacologically acceptable acid addition salts thereof. - 2 - 2,9-Oi hydro-3H-dibenzo[b, f ] -s-t r iazolo[ ,3-a]azep -ones according to claim 1 of the formula: wherein R5 an the group consisting of hydrogen and alkyl of 1 to carbon atoms, inclusive wherein R2 is selected from the group consisting of hydrogen, alkyl defined as above, in which n is a number of 1 to 4, inclusive, and R alkyl defined as above, and wherein Rg and ^ are selected from the group consisting of hydrogen and ch lcro . -44- 41277/3 -3- A compound according to claim 2, wherein R2 , R3 , R4, R5 j( and RA are hydrogen, and the compound is therefore 2,9-d ihydro-3H-dibenzo[c, f]-s-triazolo[4,3-a]azepine-;5-one . -4- A compound according to claim 2, wherein R2 is di methy l ami noethy 1 , R3 , R4, R5 , and R6 are hydrogen, and the compound is therefore 2- [2 - (d imet hy 1 am i no) ethy 1 ] -2 , 9-dihydro-3H-dtbenzo[c, fJ-s-triazolo[ ,3"a]aze i n-3"one. -5- The hydrochloride of the compound of claim 4. -6- A compound according to claim 2 , wherein R2 is 3~ (d i met hy lam i no) p ropy 1 , R3 , R4, R5 , and RE are hydrogen, and the compound is therefore 2- [3- (dimethy lami no)propy 1 ] 2, 9-d ϊ hydro-3H-d ibenzo[c, f]-s-triazo 1 o[ 4 , 3 -a ] aze i n -3- one -7- A compound accord ing to claim 2, wherein R2 is 3- (4-methy 1 -1-pi peraz i ny 1 )propy 1 , R3 , R4 , R5 , and RE are hydro gen , and the compound is therefore 2 , 9-d i hyd ro-2 - [3- (4- 41277/3 methyl-l-pipe raz i ny 1 )propy 1 ] -3H-d i benzo[ , f]-s-triazolo-[ .,3-a]azepi n- -one. -8- The compound of claim 7 as the d i hydroch lor i c acid add i t i on salt. -9" A compound according to claim 2, wherein R∑ , R3 , R5 , and R6 are hydrogen, R4 is 7"chloro and the compound is therefore 7~ch 1 oro-2 , 9-d i hyd ro-3H-d i benzo[c, ] -s- t r i azo lo-[4,3_a Jazepi n-3-one . -10- A compound according to claim 2, wherein R3 , R5i and e are hydrogen, 2 is 2- (d imethy lami no)ethy 1 , R4 is 7-chloro and the compound is therefore 7-ch loro-2- [2- (dimethylamino)ethyl]-2J9-dihydro-3H-di benzo[ c, f ] -s- 1 r i -azplo[ .,3-a Jazepi n-3-one. -11- A compound according to claim 2, wherein R2 is 2- (d i ethy lam i no)ethy 1 ; R3 , R4, R5 , and R6 are hydrogen and the compound is therefore 2- [2- (d i ethy lami no)ethy 1 ] -2, 9-d i hyd ro-3H-di benzofc, f ] - s- t r i azol o[ h, 3- a Jazep i n-3-one . -12- . The maleate of the compound of claim 11 as an acid addition salt of maleic acid. -13- A compound according to claim 2, wherein R3 is dimethylaminoethyl, R3 and R4 are hydrogen, R5 and Re are methyl and the compound is therefore 9, 9-dimethyl-2- 2-(dimethy lami no) ethy 1 ] -2 ,9-d i hydro-5H-dibenzo[c, f ]-s-t r « - 41277/2 azolo[ ,3_a ]azepi n-3~one . - - . A compound according to claim 2 as hydrochloric acid addition salt, wherein R2 is 2 - ( 1- p i e r i d i ny 1 ) ethy 1 , R3 , R4, R5, and R6 are hydrogen, and the compound is there- fore 2,9-d ihydro-2- [2- (l-p i per i d i ny 1 )ethy 1 ] ~3H-d i benzo[c, f ] -s - t r i azo 1 o , 3-a ] azep i ne-3-one hydrochloride. -15- A compound according to claim 2 as a hydrochloride wherein R2 is (l -methy 1 - p i pe r id i n -2 -y 1 )methy 1 ; R3 , R4, R5, and Re are hydrogen and the compound is therefore 2,9" d ihydro-2- [ (l-met hy 1 p i er i d i n-2- y 1 )methy 1 ] ~3H-d i benzo- [c, f ] -s - t r i azo lo[ , 3-a Jazep i n-3-one hydrochloride. -16- A compound according to claim 2 wherein R2 is 2-(methy 1 ami no )ethy 1 ; R3, R4, R5 , and RQ are hydrogen and the compound is therefore 2 , 9-d i hyd ro-2 - [2- (methy 1 am i no) -ethy 1 ] -3H-dibenzo[c, f] -s-tr iazolo[i ,3~a]azepin-3-one. -17- The hydrochloric acid addition salt of the compound of claim l6, -18- A compound according to claim 2 wherein R2, R3, R5, and Re are hydrogen, R4 is 6-chloro and the compound is therefore.6-ch 1 oro-2 , 9-d i hyd ro-3H-d i benzo[ c, f ] -s- tr i -azo 1 o[ ,3-a jazep i n-3-one . -19- A compound according to claim 2 wherein R2 is 2-(di-methy lamino)ethy 1 ; R3, R5 , and Rs are hydrogen, R4 is 6-chloro, and the compound is therefore 6-ch 1 oro-2 - [2 - (d i - 41277/2 methy lami no)ethy 1 J -2 , 9-d i hyd ro-j5H-d ibenzo[c, f]-s-tr ia ol o-[4,3-a]azepi n-3-one -20- 2-[2- (amino)ethyl J-2J9-dihydro-3H-dibenzo[c,f]-s-triazolo[4,3~a]azepi ne-3_one naps y 1 ate . -21- 2-(2- (benzylmethylamino)ethyl ]-2,9-dihydro-3H-diben-zo[c,f]-s-triazolo[4,3~a]azepine-3~one hydroch 1 or i de . -22- A compound according to claim 2 as an oxalate wherein R2 is 3~ (dimethy lamino)propy 1 , R4 is 6-chloro; R3 , R5, and Rs are hydrogen,, and the compound is therefore 6-chloro-2,9-dihydro-2-[3" (dimethylamino)propyl]-3H-dibenzo-[c,f]-s-triazolo|~4,3~a]azepin-3-one oxa late . -25- A compound according to claim 2 as a d ihyd r och 1 or i de wherein R2 is 2- (4-meth 1-1-pi peraz i ny 1 )ethy 1 , R3, R4, R5 , and Re are hydrogen, and the compound is therefore 2,9-d i hyd ro-2- [2 - (4 -me hy 1-1-piperazinyl )ethy 1 J -3H-d i benzo-[c,f]-s-triazolo[4,3-a]azepin-3-one dihydrochloride. -24- A 2,9-dihydro-3H-dibenzo[b, f]-s-triazolo[4 3-d] [l,4]-d iazepi n-3-one, according to claim 1, of the formula wherein Ri is selected from the group consisting of hy- 41277 /3 drogen · CnHgn- ; wherein n is 1 to 4, inclusive, and R is alkyl defined as above, or R1 is - Cnl^n-N. in which R-, and Rg are each selected from the group consisting of hydrogen and alkyl as defined above or together is pyrrolidine, and piperidino; wherein Pj and R^ are selected from the group consisting of hydrogen or chloro. -25 - A compound according to claim 2 , wherein j, R2 , R3, and R4 are hydrogen, and the compound is therefore 2, 9-dihydro-3H-di benzofb, f]-s-tr iazolo[4,3-d] [l,4]d iaze- pin-3-one. -26- A compound according to claim 2k wherein R2 is 2-(di meth lamino)ethyl , Ra , R3 , and R4 are hydrogen, and the compound is therefore 2- [2- (d imethy lami no)ethy 1 ] -2 , 9 - 41277/2 dihydro-3H-dibenzo[b, f ] - s - 1 r i azol o[ 4, 3-d ] [ 1, 4]d i azep i n-3-one. -27- A compound according to claim 24, wherein R2 is 3" (dimethy 1 am i no) p ropy 1 , R_ , R3, and R4 are hydrogen, and the compound is therefore 2- [3" ( imethy lamino)propy 1 ] -2,9-di hyd ro-3H-dibenzo[b, f ] - s- t r i azol o[4 , "d ] [l,4]diaze-pin-3-one. -28- A compound according to claim 24 as hydrochloride wherein Ri and R3 are hydrogen R2 is 2- (d i methy lami no) -ethyl, R4 is 7-chloro and the compound is therefore 7-ch lor 0-2- [2- (d imethy lami no )ethy 1 ] -2,9-d i hyd ro-^H-di benzo-[c,f ]-s-triazolo[4,3_aj [l.,4]diazepine-3-one hydrochloride -29- A compound according to claim 24 wherein R2 is 3- (4-methy 1 -1 -p i peraz i ny 1 )propy 1 , Ri , R3, and R4 are hydro-gen^ and the compound is therefore 2 , 9-d i ydro-2- [3- (4-methyl-l-piperazinyl )propyl]-3H-dibenzo[b, f]-s-tri azol o-[4,3-d] [l,4]diazepin-3-one. -30- The compound of claim 29 as a hydrochloric acid add i t i on sa 11. -31- A compound according to claim 24, wherein Ri is 3-(dimeth lamino)propy I ; R2, R3, and R4 are hydrogen and the compound is therefore 9- [3- (d i methy lam i no) propy 1 ] -2,9-dihydro-3H-dibenzo[b,f]-s-triazolo[4,3"d] [l,4]diaze- -50- 41277/2 -32- A compound according to claim 24, wherein Ri is methyl, R2 , 3 , and R4 are hydrogen and the compound is therefore 2,9-dihydro-9-methyl-3H-dibenzo[b,f]-s-triazolo [4, 3-d] [l, ]diazepin-3-one. -33- A compound according to claim 24, wherein Ri is methyl, R2 is 2- (dimethylamino)ethy 1 , R3 and R4 are hydrogen and the compound is therefore 2- [2- (d imethy lami no) ethy 1 ] -2, 9-d i hydro-9-methy 1 -3H-d i benzo[b, ]-s-triazolo-[4,3-d][l,4]diazepi n-3-one . - The hydrochloric acid addition salt of the compound of cla im 33 · -35- . A dibenzo[b,f]-s-triazolo[4,3-d] [l,4]oxazepin-3(2H) one, according to claim 1, of the formula: -51- 41277/4 - wherein n is 1 to 4, inclusive and R is alkyl defined as above, or R? is in which R? and R '(8 arc selected from the group consisting of hydrogen and alkyl as defined above or is pyrrolidino and piperidino; and wherein R3 and R4 are each selected from the group consisting of hydrogen or chloro. -36- A compound according to claim 35 wherein R2, R3, and R4 are hydrogen, and the compound is therefore dibenzo-fb, J-s-triazolo[ ,3:d] f l,4]oxazepin-3(2H)-one. -37- A compound according to claim 35 wherein R3 and R4 are hydrogen, R2 is 2- (d imethy lam i n'o)ethy 1 , ^and the compound is therefore 2 - [2- (d imethy lam ino)ethy 1 ]d i benzof , f ] -s-triazolo[ ,3-d][l, ]oxazepin-3(2H)-one. 41277/2 -38- A compound according to claim ¾ , wherein R3 is hydro gen, R4 is 6-chloro, R∑ is 2- (d imethy lami no)ethy 1 , and the compound is therefore 6-ch loro-2- [2- (d imethy lamino)ethy 1 ] -dibenzo[b, f ]-s-t riazolo[4,3"d] [ 1 , ] oxazep i n-3 (2H)-one . -39- A compound according to claim 35 , wherein R3 is hydro gen, R4 is 7-chloro, R2 is 2- (d imethy lami no)ethy 1 , and the compound is therefore 7-ch loro-2- [2- (d imethy lami no)ethy 1 ] -dibenzofb, f ] -s- tr iazolo[4,3"d] [l,4]oxazepin-3(2H)one . -40- A hydrochloride compound according to claim 35 wherein R3 is hydrogen, R4 is 7-chloro R2 is 3" (d imeth lami no) -propyl and the compound is therefore 7-ch loro-2- [3- (d i -met y lam?no)propylJ-dibenzo[b,fJ-s-triazolo[4,3-dJ[lJ ]-oxazep i n~ (2H )one hydrochloride. -41- A compound according to claim 35 as hydrochloride, wherein R3 and R4 are hydrogen, R2 is 3" (d imethy lami no) -propyl, and the compound is therefore 2- [3- (d imethy lami no) propy 1 Jdibenzofb, f J -s-tr i azo 1 o , 3-d ] [ 1, 4] oxazep i n-3 (2H ) -one hydrochloride. -42- A dibenzofb, f J -s - t r iazol o[4, 3-d ] [ 1 , 4] th i azep i n~3 (2H ) -one according to claim 1, of the formula: -53- in which n is 1 to defined above, or and RQ are selected from the group consisting of hydrogen and alkyl as defined above, together -N are pyrrol i- dino and piperidino; and wherein R^ and R^ are selected from the group consisting of hydrogen, chloro Inclusive, and the pharmacologically acceptable acid addition salts thereof. -43- A compound according to claim 42 wherein R?, R», and -54- 41277/ 3 R4 are hydrogen and the compound is therefore d i benzo[b, f ] -s-tr iazolo[4,3"d] [ 1, ] th i azep i n-3 (2H ) - one . -44- A compound according to claim 42, as the hydrochloride wherein R≤ is 2- (d i methy lami no)ethy 1 ; R3 and R4 are hydrogen and the compound is therefore 2 - [2- (d imeth lami no) -ethy 1 ]dibenzo[b,f ] -s - t r i azolo[ , 3-d ] [ 1 , 4 ] th i azep i n-3" (2H)one hydrochloride. -45- A compound according to claim 42, wherein R3 is hydrogen, R4 is 7-chloro, R≤ is 2- (d imethy 1 ami no)ethy 1 and the compound is therefore 7-ch loro-2- [2-(d imethy lami no)ethy 1 ] dibenzo[b, f] -s - t r i azol o[ 4, 3-d ] [ 1, 4] th iazep i n-3 (2H ) -one . -46- A compound according to claim 42,wnerejn R3 Js hydrogen, R4 is 7-chloro, R2 is 3- (d imethy lami no)propy 1 and the compound is 7- ch 1 oro-2- [3- (d i methy lami no) p ropy 1 ]d i benzo-[b,f J-s-triazolo[4,3"d] [l,4]thi azepin-3(2H)- one . -47- A process for the production of a compound selected from the group consisting of triazoloazepines of the formula III: -55- 41277/3 wherein X is selected from the group consisting of oxygen, sulfur, C in which R5 and Re are each selected from the group consisting of hydrogen and a 1 ky 1 of 1 to 3 carbon atoms inclusive; ancT^N"--^ . where R-j is hydrogen, wherein n is 1 to 4, inclusive, and R is alkyl defined above, or selected from the group consisting of hydrogen and alkyl, as is pyrrolidino and piperidino; wherein R3 and R^ are selected from the group consisting of hydrogen, chloro 41277/2 ' inclusive, which comprises: treating a compound of formu la I : wherein X, R3, and R4 are defined as above, with an alkyl- carbazate: H HaN-N-COOAlkyl wherein Alkyl is of 1 to 5 carbon atoms, inclusive, to give the corresponding compound of formula I I : wherein X, R3, and R4 are defined as above; and treating I I in the presence of a base with an alkylating agent R2CI, R2 Br or R21 wherein R2 is defined as above, to produce a compound of formula I I I above. -48- The process of claim 47 wherein the alkyl carbazate is ethyl carbazate. -49- The process of claim 47 wherein the starting com- pound I is 6(5H)morphanthridinethione and the resulting product of the first step is 2 , 9-d i hyd ro-3H-d i benzo[c, ] - s-triazolo[4,3-a]azepin-3-one. 41277/2 -50- The process of claim 47 wherein the product 2,9~di-hydro-3H-di benzo[c, f ] -s - r i azo 1 o[ 4, 3-a ]azep i n-3- one in the presence of a base is treated, with a compound selected from the group consisting of 2- (dimethylamino)ethyl chloride, 3- (diethy lamino)propyl chloride, and ch 1 orop ropy 1 ) -4-meth 1 p i peraz i ne . -51- The process of claim 47 wherein the starting compound I is 5 , 10-d ihydro-llH-d i benzo[b,e] [1, ]d iazepi ne 11-thione and the product resulting from the first step is therefore , 9-d i hyd ro-3H-d i benzo[b , f ] -s - t r i azo 1 o[4,3~d ] [l,4]diazepin-3_one. -52- The process of claim 47 wherein the product 2,9-di hydro- 3H-dibenzo[b, f]-s-triazolo[4, 3_d][l,4]diazepin-3" one in the presence of a base is reacted with a compound selected from the group consisting of 2- (d imethy lamino) ethyl chloride, 3- (d iethy lami no)propy 1 chloride, and 1-(3~ch 1 orop ropy 1 ) -4-methy 1 p i pe raz i ne . -58-