Compounds of the following formula ##STR1## are useful as central nervous system depressants, tranquilizers, sedatives, growth promotors, anti-convulsants and muscle relaxants in mammalian species.

OBJECTS OF THE INVENTION 
It is an object of the present invention to provide new compounds which are 
useful as central nervous system depressants, tranquilizers and sedatives. 
Another object is to provide methods for the preparation of these 
compounds. Another object is to provide compositions for the 
administration of the compounds of the invention. These and other objects 
of the present invention will be apparent from the following description. 
SUMMARY OF THE INVENTION 
It has now been found that 4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-ones of 
the following formula 
##STR2## 
ARE USEFUL CNS depressants, tranquilizers, sedatives, growth promotors, 
anti-convulsants and muscle relaxants in mammalian species. 
DETAILED DESCRIPTION 
The novel 4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-ones of formula 1 are 
useful CNS depressants, tranquilizers and sedatives. The novel compounds 
of formulas 3-12, and the compounds of formulas 13 and 14 some of which 
are also novel, are intermediates for the compounds of formula 1. 
##STR3## 
In the foregoing formulas 
R.sup.1 is H; phenyl; X-substituted phenyl wherein X is as defined below; 
2-, 3- or 4-pyridyl, cycloalkyl of 3-5 carbons, alkyl of 1-4 carbons 
optionally substituted by amino, by monoalkylamino of 1-4 carbons, by 
di-alkylamino of 1-4 carbons, by nitro, by cyano, by hydroxy, by alkoxy of 
1-4 carbons, by alkanoyloxy of 1-4 carbons, by phenyl wherein the phenyl 
ring is optionally substituted by one or more X groups wherein X is as 
defined below, or by a cyclic imine of formula 
##STR4## 
where D is methylene, oxygen or N-R.sup.10 and where p and q may be the 
same or different and are the integers 1, 2, and 3 provided that p + q is 
at least 1; 
R.sup.2 is H; alkyl of 1-4 carbons optionally substituted by amino, 
mono-lower alkyl, di-lower alkyl amino, cyclic imines of formula 
##STR5## 
where the cyclic imine is as defined above; hydroxy; alkoxy of 1-6 carbons 
or 
##STR6## 
where 
##STR7## 
is an acyl group capable of removal and replacement by hydrogen or alkyl 
of 1-4 carbons and R.sup.5 is alkyl of 1-5 carbons optionally substituted 
by phenyl or X-substituted phenyl; or R.sup.5 is phenyl optionally 
substituted by 1 or more X-substituents 
X and Y can be the same or different and are hydrogen, F, Cl, Br, 
trifluomethyl, alkyl of from 1-6 carbons, alkoxy of from 1-6 carbons, 
nitro, cyano, amino, alkanoylamino of 1-4 carbons, alkylthio of 1-6 
carbons, alkylsulfinyl of 1-6 carbons or alkyl sulfonyl of 1-6 carbons; 
R.sup.3 is alkyl of from 1-6 carbons, benzyl or phenethyl; 
R.sup.4 is t-butyl or benzyl optionally substituted on the phenyl ring by 
one to three X groups; 
R.sup.8 is alkyl of from 1-6 carbons, or phenyl optionally substituted by 
any alkyl, aralkyl or aryl radical compatible with cyclization to form a 
7-membered ring; 
R.sup.9 is hydrogen or alkyl of from 1-4 carbons; 
n is 0, 1 or 2; m is 0 or 1; 
R.sup.10 is hydrogen, alkyl of 1-4 carbons or phenyl optionally substituted 
by X; 
T is halogen, preferably chlorine, bromine or iodine. 
R.sup.11 is hydrogen or alkyl of 1-4 carbons; 
R.sup.12 is alkyl of 1-4 carbons substituted by the groups 
##STR8## 
where P and Q may be the same or different and may be hydrogen, phenyl, 
X-substituted phenyl, naphthyl or X-substituted naphthyl, with the proviso 
that at least one of P and Q is one of the foregoing aryl radicals, 
R.sup.13 is alkyl of 1-6 carbons. 
Preferably, R.sup.1 is hydrogen, cycloalkyl of 3-5 carbons, or alkyl of 1-4 
carbons optionally substituted by amino, nitro, cyano, hydroxy, alkoxy of 
1-4 carbons, alkanoyloxy of 1-4 carbons, mono-alkylamino of 1-4 carbons, 
dialkylamino of 1-4 carbons or by a cyclic imine of formula 
##STR9## 
where D, p and q are as previously defined. Most preferably, R.sup.1 is 
hydrogen or alkyl of 1-4 carbons. 
Preferably, R.sup.2 is hydrogen, alkyl of 1-4 carbons or hydroxy. 
Preferably, R.sup.8 is alkyl of 1-4 carbons. The radical R.sup.8 as well as 
the oxygen atom to which it is bonded are removed during cyclization. 
Synthesis 
The 4-H-s-triazolo[4,3-a][1,5]benzodiazepin-5-ones of formulas 1 and 11 can 
be prepared by several methods. 
One method (hereinafter called the first method) involves reacting a 
compound of formulas 3-6 with from about 0.8 to about 6.0, preferably from 
about 1.0 to about 3.0 molar equivalents of an acid hydrazide of formula 
##STR10## 
(where R.sup.1 is as defined previously) in an inert, organic solvent or 
mixture of solvents. Typical organic solvents which may be used in the 
above reaction include aryl hydrocarbons, e.g., benzene, toluene, xylene 
and the like; chlorinated hydrocarbons such as di-, tri-, 
tetrachloroethanes and the like; lower molecular weight alkanols of 1-6 
carbons such as methanol, ethanol, tertiary butyl alcohol, n-butanol and 
the like; N,N-dialkylformamides, N,N-dialkyl alkanoyl amides wherein the 
alkyl and alkanoyl radicals have 1-4 carbons, such as dimethylformamide, 
dimethylacetamide and the like; hexamethylphosphorous triamide, ethers, 
such as dioxane and the like and di-lower alkyl sulfoxides, such as 
dimethyl sulfoxide and the like. The reaction is carried out at from about 
40.degree. C to about 250.degree. C, preferably from about 60.degree. C to 
about 180.degree. C, until a significant amount of end product is 
obtained, typically, for from about 1/4 to about 92 hours, preferably from 
about 1 to about 48 hours. 
The final product of formula 1 or 11 is isolated by conventional 
techniques. For example, the reaction mixture is evaporated and the 
residue is partitioned between aqueous sodium bicarbonate and a 
water-immiscible inert, organic solvent, such as halogenated hydrocarbons, 
e.g., methylene chloride, chloroform or trichloroethylene; alkyl esters 
wherein both the acid and alcohol from which the ester is derived may have 
from 1 to 4 carbon atoms, e.g., ethyl acetate, propyl acetate, ethyl 
propionate and the like. The organic solvent is washed with water, dried 
and chromatographed. 
A compound of formula 12 may be converted to the corresponding compound of 
formula 1 by another method for the synthesis of compounds of formula 1 
where R.sup.1 is alkyl substituted by amino, mono-alkyl amino or a hydroxy 
group. Such a method involves reacting a compound of formula 12 with 
appropriate reagents under appropriate conditions as described below 
suitable for the selective replacement of the 
##STR11## 
or the 
##STR12## 
by a hydrogen atom. 
One such method involves reacting the compounds of formula 12 with at least 
about 0.5 preferably at least about 0.8, molar equivalent of an inorganic 
hydrogen halide (preferably hydrogen chloride, hydrogen bromide and 
hydrogen fluoride) or with a halogenated lower alkyl carboxylic acid 
(preferably trifluoroacetic acid). The reaction is run in anhydrous 
hydrogen fluoride, or, when employing other acids, in an optional inert 
solvent. 
Typical solvents include lower carboxylic acid such as acetic acid and the 
like; ethers such as diethyl ether, dioxane, tetrahydrofuran and the like; 
lower molecular weight alkanols of 1-6 carbons such as methanol, ethanol, 
and the like; alkyl esters wherein both the acid and the alcohol from 
which the ester is derived may have from 1-4 carbon atoms such as ethyl 
acetate, propyl acetate, ethyl propionate and the like; halogenated 
hydrocarbons such as methylene chloride, chloroform, di-, tri- and 
tetrachloroethanes and the like; nitroalkanes of 1-4 carbons such as 
nitromethane, nitroethane and the like; or lower alkyl ketones of 2-5 
carbons such as acetone, methylethyl ketone and the like. 
The reaction is carried out at from about -50.degree. C to about 
200.degree. C, preferably from about 0.degree. C to about 120.degree. C, 
until a significant amount of end product is obtained, typically, for from 
about 1/10 to about 92, preferably from about 1/6 to about 30 hours. The 
corresponding product of formula 1 is isolated by conventional techniques. 
For example, with all acids except hydrogen fluoride, the reaction mixture 
is diluted with an inert water-immiscible organic solvent, washed with 
dilute aqueous sodium bicarbonate, dried and chromatographed. When using 
hydrogen fluoride, the hydrogen fluoride is evaporated, the residue 
dissolved in an inert organic solvent, such as halogenated hydrocarbons, 
e.g., methylene chloride, chloroform or trichloroethylene; alkyl esters 
wherein both the acid and the alcohol from which the ester is derived may 
have from 1-4 carbon atoms, e.g., ethylacetate, propyl acetate, ethyl 
propionate and the like, washed with water, dried and chromatographed. 
Another such method for the selective replacement of the 
##STR13## 
by hydrogen is compounds of formula 12 involves the reaction of said 
compounds of formula 12 with hydrogen in the presence of an appropriate 
catalyst, in an inert organic solvent. Typical catalysts include platinum, 
Raney nickle and, preferably, palladium. Typical solvents include lower 
alkanols of 1-6 carbons such as ethanol, methanol, and the like; formic 
acid; lower alkanoic acids of 2-5 such as acetic acid and the like as well 
as other typical solvents well known to those versed in the art. Typical 
hydrogenation pressures are from about 0.1 to about 2000 atmospheres, 
preferably from about 0.8 to about 100 atmospheres. The reactions are 
carried out for from about 1/2 to about 96 hours, preferably from about 1 
to about 72 hours at from about 0.degree. C to about 200.degree. C, 
preferably from about 20.degree. C to about 120.degree. C. The products 
are isolated in a conventional manner. For example the catalyst is 
filtered off, the solvent evaporated and the product chromatographed. 
Another method for the synthesis of compounds of formulas 1 and 11 involves 
heating compounds of formula 7 either alone or in an inert, organic 
solvent at from about 60.degree. C to about 350.degree. C, preferably from 
about 80.degree. C to about 300.degree. C for about 1/2 to about 72 hours, 
preferably from about 1 to about 24 hours. Typical inert, organic solvents 
that are used are those defined in the first method. The products are 
isolated by conventional techniques. For example, the reaction is diluted 
with a water-immiscible inert, organic solvent, washed with water dried 
and chromatographed. 
Another method (hereinafter called the fifth method) of synthesis for 
compounds of formulas 1 and 11 involves reacting compounds of formula 8 
with from about 0.8 to about 6, preferably from about 1 to about 3, molar 
equivalents of acyl derivatives of formula 
##STR14## 
in an optional inert organic solvent. Typical inert organic solvents which 
may be used includes aryl hyrocarbons such as benzene, toluene, xylene and 
the like; chlorinated hydrocarbons such as tri- and tetrachloroethanes and 
the like; ethers such as 1,2dimethoxyethane tetrahydrofuran, dioxane and 
the like; N,N-dialkylformamides and alkyl alkanoylamides wherein the alkyl 
and alkanoyl radicals have 1-4 carbons such as dimethylformamide, 
dimethylacetamide and the like. Where W is lower alkoxy or hydroxy, 
suitable solvents also include lower alkanols of 1-6 carbons such as 
ethanol, t-butyl alcohol and n-butyl alcohol and the liked and dimethyl 
sulfoxide. The reaction conditions and the isolation of the products are 
as described in the first method. 
Another method for the synthesis of compounds of formulas 1 and 11 involve 
reacting compounds of formula 9 with at least about 0.1 preferably from at 
least about 0.8 to about 3 molar equivalents of an acyl derivative of 
formula 
##STR15## 
in the presence of at least about 0.1, preferably from at least about 0.8 
to about 3, molar equivalents of an inorganic hydrohalic acid, preferably 
hydrogen bromide or hydrogen chloride. The reaction can optionally be run 
in an inert organic solvent. Where compounds of formula 
##STR16## 
are "strong" carboxylic acids, such as chloroacetic, trifluoroacetic and 
oxalic acid and the like, the use of a hydrohalic acid is optional. 
Typical inert organic solvents include lower molecular weight ethers such 
as 1,2 -dimethoxyethane, dioxane, tetrahydrofuran and the like; 
halogenated hydrocarbons such as methylene chloride, di-, tri-, and 
tetrachloroethane and the like; nitroalkanes of 1-4 carbons such as 
nitromethane, nitroethane and the like; lower alkanols of 1-6 such as 
ethanol, n-butanol and the like. The reaction is carried out at from about 
-50.degree. C to about 250.degree. C, preferably from about +10 to about 
180.degree. C, for from about 1/4 to about 96 hours, preferably from about 
1/2 to about 48 hours. The products are isolated using conventional 
techniques as described in the first method. 
Compounds of formula 1 where R.sup.1 is lower acyloxy 
##STR17## 
can be prepared by reacting compounds of formula [1, where R.sup.2 is 
halogen, with the appropriate acid of formula 
##STR18## 
(or alkali metal or tri-lower alkyl amine salt thereof) or with the 
appropriate alcohol of formula HOR.sup.13 (or alkali metal salt thereof), 
respectively. The reaction is run in excess acid or alcohol, respectively, 
or, optionally, in an inert organic solvent such as ethers such as 
dioxane, tetrahydrofuran, 1,2-dimethoxyethane and the like; 
N,N-dialkylformamides, N,N-dialkylalkanoyl amides wherein alkyl and 
alkanoyl radicals have 1-4 carbons, such as dimethyl formamide, 
dimethylacetamide and the like. The reaction is carried out for from about 
1/4 to about 72 hours, preferably about 1/2 to about 12 hours, at from 
about -20.degree. C to about 150.degree. C, preferably about 20.degree. C 
to about 100.degree. C. The products are isolated by conventional 
techniques as described in the first method. 
The compounds of formula 1 where R.sup.2 .dbd.OH are obtained by reacting 
compounds of formula 1 where R.sup.2 is 
##STR19## 
with from about 0.2 to about 6, preferably about 0.8 to about 3, molar 
equivalents of an alkali metal (preferably sodium and potassium) 
hydroxide, bicarbonate or carbonate in an inert organic solvent, in 
optional presence of water. Suitable organic solvents include lower 
molecular weight alcohols, such as methanol, ethanol and the like; 
water-miscible ethers such as tetrahydrofuran, 1,2-dimethoxyethane, 
dioxane and the like; N,N-dialkylformamides, N,N-dialkyl alkanoylamides 
wherein the alkyl and alkanoyl radicals have 1-4 carbons such as 
dimethylformamide, dimethylacetamide, and the like. The reaction is 
carried out at from about -50.degree. C to about 100.degree. C, preferably 
about -20.degree. C to about 70.degree. C, for from about 1/4 to about 72 
hours, preferably about 1/2 to about 24 hours. The products are isolated 
in a conventional manner. For example, the reaction mixture is neutralized 
with acetic acid, evaporated and chromatographed. 
The compounds of formula 1 where R.sup.2 is halogen (preferably bromine or 
chlorine) are prepared by reacting compounds of formula 1 where R.sup.2 
with from about 0.5 to about 3, preferably from about 0.8 to about 1.3, 
molar equivalents of a lower alkyl N-haloamide, lower cycloalkyl 
N-haloimide or aryl sulfonyl N-haloamide, in the presence of a free 
radical catalyst, in an inert organic solvent. Suitable N-halo amides and 
imides include N-chloro and N-bromo-succinimide, and the like; 
N-chloroacetamide and the like; and N-chlorobenzenesulfonamide and the 
like. Suitable free radical catalysts include azobis-lower alkyl nitriles 
such as the preferred catalyst, azebisisobutyronitrile; di-lower alkyl 
peroxides such as di-t-butylperoxide; di-acyl peroxides such as acetyl 
peroxide; per esters such as t-butylperbenzoate; hydroperoxides such as 
t-butyl-hydroperoxide and the like. Typical inert organic solvents are 
aromatic hydrocarbons, such as benzene, toluene, xylene and the like; and 
chlorinated hydrocarbons such as methylene chloride, chlorobenzene, carbon 
tetrachloride, di-, tri- and tetrachloroethanes, chlorobenzene, and the 
like. The reaction is carried out at from about 25.degree. C to about 
200.degree. C, preferably at about the reflux temperature of the reaction 
medium, for from about 1/4 to about 24 hours, preferably for from about 
1/2 to about 5 hours. The product is isolated by conventional techniques. 
For example, the reaction mixture cooled to room temperature and 
evaporated. 
Compounds of formula 1 where R.sup.2 is alkyl of 1-4 carbons substituted by 
amino are prepared by reacting compounds of formula 1 where R.sup.2 is 
hydrogen with from about 0.5 to about 12, preferably from about 0.8 to 
about 3.0 molar equivalents of an appropriate base, followed by reaction 
of the thus formed salt with a corresponding molar equivalent of an 
appropriate amino alkyl alkylating agent of formula R.sup.6 -M where 
R.sup.6 is the amino alkyl moiety and M is halogen, preferably chlorine, 
bromine, iodine; 
##STR20## 
or an alkyl or arylsulfonate of formula 
##STR21## 
where R.sup.7 can be alkyl of 1-6 carbons or aryl of from about 6 to 10 
carbons optionally substituted by halogen, nitro or alkyl of 1-3 carbons, 
or R.sup.6 -M may be any other agent (within the definition of R.sup.6) 
capable of introducing an aminoalkyl group. The reaction is run in an 
essentially inert organic solvent. 
Typical bases include alkali metal (preferably sodium and potassium) salts 
as well as thallous salts of lower molecular weight alkanols of 1-6 
carbons such as methanol, ethanol, propanol, isopropal, t-butanol, amyl 
alcohol and the like; alkali metal (preferably sodium) hydrides; alkali 
metals (preferably sodium and potassium); alkali metal (preferably sodium 
and potassium) salts of acidic hydrocarbons such as triphenylmethane and 
the like as well as any other base known to those skilled in the art for 
generating salts of acidic methylene groups. Typical organic solvents 
include those described in the first method. 
The reaction is carried out at from about -20.degree. C to about 
300.degree. C, preferably from about 0.degree. C to about 100.degree. C 
for from about 0.2 hours to about 96 hours, preferably from about 0.5 hour 
to about 72 hours. 
The products of formula 1 where R.sup.2 is alkylamino are isolated by 
conventional techniques. For example the reaction mixture is evaporated; 
the residue is diluted with a water-immiscible, inert solvent such as 
methylene chloride, washed with water, dried and chromatographed. 
Compounds of formula 1 can also be prepared by reacting compounds of 
formula 10 with at least from about 0.5 to a large excess, preferably at 
least from about 0.8 to about 100, molar equivalents of an aryl halide, in 
the presence of a copper catalyst, in an appropriate solvent containing 
from about 0.5 to about 1000, preferably about 0.8 to about 100, molar 
equivalents of an appropriate hydrogen halide acceptor. The preferred aryl 
halides are those of formula AR-K where AR is phenyl optionally 
substituted by X and where K is preferably chlorine, bromine or iodine. 
The preferred copper catalysts are powdered copper metal, copper oxides 
and cuprous and cupric salts. Typical solvents include 
N,N-dialkylformamides and N,N-dialkyl alkanoyl amides wherein the alkyl 
and alkanoyl radicals have 1-4 carbons such as N,N-dimethylformamide, 
N,N-dimethylacetamide and the like; dialkyl sulfoxides of 2-6 carbons such 
as dimethyl sulfoxide and the like; and alkylphosphorous triamides of 4-10 
carbons such as hexamethylphosphorous triamide. Appropriate hydrogen 
halide acceptors include alkali metal (preferably sodium or potassium) 
carbonates, bicarbonates, or lower alkyl carboxylic acid salts thereof 
(e.g., acetates). The reaction is carried out at from about 50.degree. C 
to about 200.degree. C, preferably at from about 90.degree. C to about 
180.degree. C, for from about 1/4 to about 72 hours, preferably for from 
about 1/2 to about 14 hours. The product is isolated in a conventional 
manner. For example, the reaction mixture is diluted with methylene 
chloride, washed with dilute aqueous ammonium hydroxide and 
chromatographed. 
Compounds of formula 2 where m is one are prepared by reacting compounds of 
formula 17 where m is one with from about 0.5 to about 10, preferably 
about 0.8 to about 2, molar equivalents of a malonyl dihalide (preferably 
malonyl dichloride or malonyl dibromide) or an alkyl malonic acid 
derivative (of formula 
##STR22## 
in an inert organic solvent. Typical solvents are aromatic hydrocarbons 
such as benzene, toluene, xylene and the like; certain ethers such as 
dioxane, 1,2-dimethoxyethane, tetrahydrofuran and the like; chlorinated 
hydrocarbons such as di-, tri- and tetra-chloroethanes, chloroform, 
chlorobenzene, CCl.sub.4, dichloroethane and the like; 
N,N-dialkylformamides and N,N-dialkyl alkanoylamides wherein the alkyl and 
alkanoyl radicals have 1-4 carbons such as N,N-dimethylformamide, 
N,N-dimethylacetamide and the like. 
The reaction is carried out at from about -10.degree. C to about 
200.degree. C, preferably at from about +10.degree. C to about 140.degree. 
C, for from about 1/4 to about 92 hours, preferably for from about 1 to 
about 24 hours. The products are isolated in a conventional manner. For 
example, the solvent is partially evaporated and the product filtered off. 
Compounds of formula 2 where m is one are also prepared by reacting 
compounds of formula 17 where m is one with from about 0.5 to about 3, 
preferably from about 0.8 to about 1.4, molar equivalents of a malonic 
acid of the formula 
##STR23## 
in an aqueous mineral acid. Typical mineral acids include sulfuric, 
hydrobromic and hydrochloric acid. The concentration of acid is from about 
2 to about 7 normal, preferably from about 3.5 to about 4.5, normal. The 
reaction is carried out for from about 1/4 to about 92 hours, preferably 
for from about 1/2 to about 24 hours at from about 40.degree. C to about 
200.degree. C, preferably from about 60.degree. C to about 140.degree. C. 
The product is isolated in a conventional manner. For example, the 
reaction is cooled and the product filtered off. 
Compounds of formula 2 where m is one are also prepared by reacting 
compounds of formula 13 where m is one in the optional presence of a 
catalyst in the optional presence of water in an organic solvent. Typical 
catalysts include inorganic acids such as hydrogen chloride, hydrogen 
bromide and sulfuric acid as well as bases such as alkali metal 
(preferably sodium and potassium) hydroxides and lower alkoxides and other 
conventional bases used for the condensation of an aryl amine with an 
alkyl carboxylic acid ester. Typical solvents include alkanols of 1-6 
carbons such as methanol, ethanol and the like; certain water-miscible 
ethers such as tetrahydrofuran, dioxane and the like; 
N,N-dialkylformamides and N,N-dialkyl alkanoyl amides wherein the alkyl 
and alkanoyl radicals have 1-4 carbons such as N,N-dimethyl formamide, 
dimethylacetamide and the like. The reaction is carried out for from about 
1/2 to about 96 hours, preferably for from about 1 to about 24 hours at 
from about -20.degree. C to about 150.degree. C, preferably 0.degree. C to 
100.degree. C. The product is isolated in a conventional manner. For 
example the reaction is neutralized, diluted with a water-immiscible inert 
organic solvent, washed with water, dried and chromatographed. 
Compounds of formula 2 where m is one are also prepared by reacting 
compounds of formula 14 where m is one with an appropriate reducing agent, 
in the presence of an acid or base catalyst, in the optional presence of 
water in an organic solvent. Typical reducing systems include powdered 
iron, zinc and tin in the presence of an aqueous acid, in an optional 
organic solvent. Typical acids include hydrohalic acids (preferably 
hydrochloric acid) and alkyl carboxylic acids of 1- 6 carbon atoms such as 
acetic acid and the like. Typical solvent systems include aqueous alkanols 
of 1- 6 carbons such as methanol, ethanol and the like. Still other 
reducing agents include stannous chloride and aqueous hydrochloric acid; 
sodium hydrosulfite; ferrous sulfate and ammonium hydroxide; ammonium 
sulfide; hydrazine in the presence of palladized charcoal; sodium sulfide 
and ammonium chloride, sodium sulfide and sulfur. The reaction is carried 
out at from about 0.degree. C to about 200.degree. C, preferably at from 
about 10.degree. C to about 140.degree. C for from about 1/6 to about 92 
hours, preferably for from about 1/2 to about 24 hours. The products are 
isolated by conventional techniques. For example the reaction is filtered, 
evaporated, saponified in alcoholic potassium hydroxide, evaporated, taken 
up in water, adjusted to pH 6 and the product filtered off and 
chromatographed. 
Compounds of formula 2, where m is zero are prepared from compounds of 
formulas 13, 14 and 17 where m is zero by the methods described for the 
preparation of compounds of formula 2, where m is one [see also: Chemical 
Reviews, 68, 780ff( 1968) and references cited therein and, S. African 
patent 6800803 (1968)]. 
Compounds of formula 3 can be prepared by reacting compounds of formula 2 
with from about 0.5 to about 2.0, preferably with from about 0.9 to about 
1.2, molar equivalents of phosphorous pentasulfide in an aprotic, 
essentially inert organic solvent. Typical inert organic solvents include 
aryl hydrocarbons such as benzene, toluene or xylene; aliphatic 
hydrocarbons of 5-12 carbons, such as hexane, heptane and the like; 
alicyclic hydrocarbons of 5-8 carbons, such as cyclohexane and the like; 
basic carbocyclic amines such as pyridine, quinoline, .gamma.-picoline and 
the like; and any other conventional solvent materials which are 
relatively inert with regard to the starting materials. 
The reaction is carried out at from about 10.degree. C to about 250.degree. 
C, preferably at from about 50.degree. C to about 150.degree. C, for from 
about 5 minutes to about 72 hours, preferably from about 10 minutes to 
about 6hours. The product of formula 3 is isolated by conventional 
techniques. For example the reaction solvent is evaporated, the residue 
stirred with ice water, extracted into a water-immiscible organic solvent; 
the water-immiscible solvent is washed consecutively with water, dilute 
aqueous hydrohalic acid, dried and chromatographed. 
Compounds of formula 4 are prepared by reacting compounds of formula 3 with 
from about 0.5 to about 6, preferably from about 0.8 to about 1.2, molar 
equivalents of an alkylating agent of formula R.sup.3 -M [where M may be 
halogen, preferably bromine or iodine 
##STR24## 
or an alkyl or arylsulfonate moiety of formula 
##STR25## 
where R.sup.7 can be alkyl of 1-6 carbons or aryl of from 6 to 10 carbons 
optionally substituted by halogen, nitro or alkyl of 1-3 carbons or 
R.sup.3 -M may be any other agent (within the definition of R.sup.3) 
capable of selectively alkylating the sulfur atom in the presence of the 
other groups in 3] in the presence of an appropriate base in an inert 
organic solvent. Typical bases include alkali metal hydroxides (preferably 
sodium and potassium hydroxide), alkali metal carbonates (preferably 
sodium and potassium bicarbonate or carbonate) and appropriate organic 
tertiary amines such as trialkylamines, e.g., triethylamine and the like, 
and pyridine and the like. Typical solvents include lower molecular weight 
alkanols of 1-6 carbons such as methanol, ethanol and the like; 
water-miscible ethers such as dioxane, tetrahydrofuran, 
1,2-dimethoxyethane and the like; N,N-dialkylformamides and N,N-dialkyl 
alkanoyl amides wherein the alkyl and alkanoyl radicals have 1-4 carbon 
atoms such as dimethyl formamide or dimethylacetamide and the like; alkyl 
ketones of 2-5 carbons such as acetone, methylethylketone and the like, 
and dimethyl sulfoxide. The reaction is carried out at from about 
-60.degree. C to about 150.degree. C, preferably at from about 0.degree. C 
to about 90.degree. C, for from about 1 minute to about 90 hours, 
preferably for from about 5 minutes to about 24 hours. The products of 
formula 4 are isolated by conventional techniques. For example, the 
reaction is diluted with water, extracted with a water-immiscible solvent, 
dried and chromatographed. 
Compounds of formula 5 can be prepared by reacting compounds of formula 2 
with from about 0.5 to about 3, preferably with from about 0.8 to about 
1.2, molar equivalents of a suitable halogenating agent in an inert 
organic solvent, in the optional presence of an acid proton acceptor. 
Typical halogenating agents include the phosphorous halides such as 
phosphorous pentachloride, phosphorous oxychloride, and phosphorous 
oxybromide. Typical inert organic solvents include aromatic hydrocarbons 
such as benzene, toluene xylene and the like; chlorinated hydrocarbons 
such as methylene chloride, chloroform, chlorobenzene, CC1.sub.4, di-, 
tri- and tetrachloroethanes and the like. Phosphorous oxyhalides such as 
phosphorous oxychloride and the like can be used both as solvent and 
halogenating agent. 
Optional acid proton acceptors include N,N-di-lower alkyl aryl amines such 
as N,N-dimethylaniline, N,N-diethylaniline and the like and trialkylamines 
such as triethylamine, tributylamine and the like. 
The reaction is carried out at from about 0.degree. C to about 200.degree. 
C, preferably at from about 40.degree. C to about 150.degree. C, for from 
about 1/4 to about 72 hours, preferably for from 178 to about 24 hours. 
The products of formula 5 are isolated by conventional techniques. For 
example, the reaction mixture is evaporated and the residue is diluted 
with an aprotic, inert, organic solvent, washed with cold water, and then 
evaporated. The residual product is stirred with a non-solubilizing inert 
organic solvent, such as carbon tetrachloride, and the product is filtered 
off. 
Compounds of formula 6 are prepared by reacting compounds of formula 2 with 
from about 0.8 to about 50, preferably about 1 to about 20, molar 
equivalents of a diazo-lower alkane in an inert organic solvent. Typical 
inert organic solvents include lower molecular weight ethers such as 
diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; 
alkanols of 1-6 carbons such as methanol, ethanol and the like and 
halogenated hydrocarbons such as chloroform methylene chloride, CC1.sub.4, 
1,2-dichloroethane, chlorobenzene, di-, tri- and tetrachloroethanes and 
the like. 
The reaction is carried out at from about -50.degree. C to about 
100.degree. C, preferably at from about 0.degree. C to about 60.degree. C 
for from about 1/4 hour to about 72 hours preferably for from about 1/2 to 
about 12 hours. 
The products of formula 6 are isolated by conventional techniques. For 
example, the reaction is filtered, evaporated and chromatographed. 
Another method for the preparation of compounds of formula 6 involves 
reacting compounds of formula 2 with from about 0.5 to about 3, preferably 
with from about 0.8 to about 1.4, molar equivalents of a tri-lower alkyl 
oxonium fluoroborate in an inert organic solvent. Typical solvents include 
halogenated hydrocarbons such as methylene chloride, CC1.sub.4, 
chloroform, 1,2-dichloroethane, chlorobenzene, di-, tri- and 
tetrachloroethanes and the like. The reaction is carried out at from about 
-50.degree. C to about 100.degree. C, preferably at from about -20.degree. 
C to about 70.degree. C for from about 178 hour to about 72 hours 
preferably for from about 1 to about 24 hours. 
The products of formula 6 are isolated by conventional techniques. For 
example, the reaction mixture is washed with cold aqueous potassium 
bicarbonate, dried and the solvent evaporated. 
Compounds of formula 7 are prepared by reacting compounds of formulas 3-6 
with from about 0.8 to about 6.0, preferably with from about 1 to about 3, 
molar equivalents of an acid hydrazide of formula 
##STR26## 
in an inert organic solvent. Typical solvents include alkanols of 1-6 
carbons such as methanol, ethanol, t-butanol, n-butanol and the like; 
aromatic hydrocarbons such as benzene, toluene, xylene and the like; 
chlorinated hydrocarbons such as methylene chloride, chloroform, di-, tri- 
and tetrachloroethane and the like; ethers such as tetrahydrofuran, 
dioxane, 1,2-dimethoxyethane and the like; N,N-dialkylformamides, 
N,N-dialkyl alkanoyl amides wherein the alkyl and alkanoyl radicals have 
from 1-4 carbons, such as N,N-dimethyl formamide, N,N-dimethylacetamide 
and the like; hexamethylenephosphorous triamide and dimethyl sulfoxide. 
The reaction is carried out at from about -30.degree. C to about 
160.degree. C preferably at from about 30.degree. C to about 120.degree. 
C, for from about 1/2 to about 96 hours, preferably for from about 2 to 
about 12 hours. The products of formula 7 are isolated by conventional 
techniques. For example, the reaction is diluted with a water-immiscible 
inert organic solvent, washed with water, dried and chromatographed. 
Compounds of formula B are prepared by reacting compounds of formula 9 with 
at least about 0.1 preferably from about 0.8 to about 3, molar equivalents 
of an inorganic hydrohalic acid, preferably hydrogen bromide or hydrogen 
chloride in an inert organic solvent. Typical inert organic solvents 
include alkanols of 1-6 carbons such as ethanol, t-butanol and the like; 
lower molecular weight ethers such as dioxane, tetrahydrofuran, diethyl 
ether, 1,2-dimethoxyethane and the like; chlorinated hydrocarbons such as 
methylene chloride, CC1.sub.4, chlorobenzene, di-, tri-, and 
tetrachloroethanes, chloroform and the like; N,N-dialkylformamides, 
N,N-dialkyl alkanoyl amides wherein the alkyl and alkanoyl radicals have 
1-4 carbons, such as dimethyl formamide, dimethylacetamide and the like. 
The reaction is run for from about 174 to about 90 hours, preferably for 
from about 178 to about 3 hours, at from about -50.degree. C to about 
100.degree. C, preferably at from about -30.degree. to about 80.degree. C. 
For example, the solvent is evaporated at room temperature in vacuo, the 
residue stirred in cold water containing an alkali metal hydroxide, 
equivalent in molar amount to the amount of hydrohalic acid used, and the 
product is then removed by filtration and dried. 
Compounds of formula 9 are prepared by reacting compounds of formulas 3-6 
with from about 0.5 to about 6, preferably with from about 0.8 to about 3, 
molar equivalents of a compound of formula 
##STR27## 
in an inert organic solvent. Typical solvents are those as defined in the 
first method. The reaction is carried out at from about 40.degree. C to 
about 250.degree. C, preferably at from about 50.degree. C to about 
180.degree. C for from about 1/4 hours to about 92 hours, preferably about 
1 to about 48 hours. The products of formula 9 are isolated by 
conventional techniques as described in the first method. 
Compounds of formula 10 are prepared by the removal of the N.sup.6 benzyl 
group in compounds of formula 11 wherein the benzyl group is replaced by 
hydrogen. Suitable reagents and conditions are those described below for 
the debenzylation of compounds of formula 12. The isolation of the 
products is as exemplified for compounds of formula 12. 
Compounds of formula 12 are prepared by reacting compounds of formulas 3-6 
wherein m is zero with from about 0.5 to about 6, preferably with from 
about 0.8 to about 3, molar equivalents of an acid hydrazide of formula 
##STR28## 
in an inert organic solvent. Typical solvents, the conditions of the 
reaction and the isolation of the product are as described in the first 
method. 
Compounds of formula 13 are prepared by reacting compounds of formula 14 
with an appropriate reducing agent under selective conditions in an inert 
organic solvent. 
Typical reducing agents include a metal catalyst, preferably Raney nickel, 
and hydrogen in the optional presence of a hydrogen halide in an inert 
organic solvent. Typical solvents include alkanols of 1-6 carbons such as 
methanol, ethanol and the like. The preferred optional hydrogen halides 
are hydrogen chloride and hydrogen bromide. The reactions are carried out 
for from about 1/6 hour to about 92 hours, preferably for from about 178 
to about 24 hours at from about 0.degree. C to about 150.degree. C, 
preferably at from about 10.degree. C to about 120.degree. C. Hydrogen 
pressures are from about 0.1 to about 100 atm. preferably about 0.8 to 
about 10 atm. The reaction is stopped after approximately three molar 
equivalents of hydrogen have been absorbed. The products are isolated in a 
conventional manner. For example the reaction is filtered, made alkaline 
to pH 8, extracted with a water-miscible organic solvent, washed with 
water, dried and chromatographed. 
Compounds of formula 14 are prepared by reacting compounds of formula 15 
with from about 0.5 to about 6, preferably with from about 0.8 to about 2, 
molar equivalents of a compound of formula 16 (where B is halogen, 
preferably chlorine or bromine, or a group of formula 
##STR29## 
in an inert organic solvent. Typical solvents include aromatic 
hydrocarbons such as benzene, toluene, xylene and the like; halogenated 
hydrocarbons such as chloroform, methylene chloride, CC1.sub.4, 
chlorobenzene, di-, tri- and tetrachloroethane and the like; certain 
ethers such as 1,2-dimethoxyethane, dioxane, tetrahydrofuran and the like; 
N,N-dialkylformamides, N,N-dialkyl alkanoyl amides wherein the alkyl and 
alkanoyl radicals have 1-4 carbons, such as N,N-dimethyl amide and the 
like. The reactions are carried out for from about 178 to about 92 hours, 
preferably for from about 2 to about 24 hours at from about -20.degree. C 
to about 150.degree. C, preferably at from about +5.degree. C to about 
100.degree. C. The products are isolated by conventional techniques as 
exemplified in the first method. 
Compounds of formula 17 are prepared by reacting compounds of formula 15 
with an appropriate reducing agent in an essentially inert organic 
solvent. Typical reducing agents include a metal catalyst such as 
palladium, platinum and the preferred catalyst Raney nickel in the 
presence of hydrogen in the optional presence of a hydrogen halide 
(preferably hydrogen chloride and hydrogen bromide). Typical solvents 
include alkanols of 1 to 6 carbons such as methanol, ethanol, propanol, 
isopropanol and the like. 
Hydrogen pressures are from about 0.1 to about 100 atm., preferably from 
about 0.8 to about 10 atm. The reaction is stopped after approximately 
three molar equivalents of hydrogen have been absorbed. 
The reaction is carried out at from about 0.degree. C to to about 
150.degree. C, preferably from about 20.degree. C to about 100.degree. C 
for from about 0.2 to about 96 hours, preferably from about 0.5 hour to 
about 24 hours. 
The products of formula 17 are isolated by conventional techniques. For 
example the reaction is filtered, made alkaline to pH 8, diluted with a 
water-immiscible, inert organic solvent, washed with water, dried and 
evaporated. 
Compounds of formula 15 are prepared by reacting compounds of formula 18 
with at least about 0.2 molar equivalents, preferably from about 0.8 to 
about 100 molar equivalents of a compound of formula 19 in the optional 
presence of a hydrogen halide acceptor in the optional presence of an 
inert organic solvent. 
Typical hydrogen halide acceptors include alkali metal (preferably sodium 
or potassium) carbonates, bicarbonates, or lower alkyl carboxylic acid 
salts thereof (e.g., acetates). 
Typical solvents include nitrohydrocarbons such as nitrobenzene and the 
like; lower alkanols of 1-6 carbons such as ethanol, t-butanol, butanol 
and the like. 
The reaction is carried out at from about 25.degree. C to about 300.degree. 
C, preferably from about 50.degree. C to about 250.degree. C for from 
about 0.2 hour to about 96 hours, preferably from about 1 hour to about 48 
hours. 
The products of formula 15 are isolated by conventional techniques. For 
example the reaction is poured into excess dilute hydrochloric acid and 
extracted with ether. For products of formula 15 where m is zero, the 
ether is dried, evaporated and the residual crude product is 
chromatographed. 
For products of formula 15 where m is one, the above obtained aqueous 
hydrochloric acid extract is made alkaline to pH 9 and extracted with 
ether. The ether is dried, evaporated and the residual product is 
chromatographed. 
For compounds of formula 15 where m is zero see also Chemical Abstracts, 
43, 6175d (1948). 
For compounds of formula 15 where m is one see also Proc. Indian Acad. 
Sci., 47A, 77 (1958). 
For compounds of formula 16 see Acta Chem. Scand., 15,260 (1961). 
The novel compounds of formula I are CNS depressants and are useful as, for 
example, sedatives, tranquilizers, hypnotics, anticonvulsants and muscle 
relaxants in mammalian species, e.g. rats, mice and monkeys. They are also 
useful as feed additives for increasing growth rate and feed efficiency in 
mammalian species, such as livestock, specifically swine and cattle. The 
CNS depressant effects of compounds of this invention are shown, for 
example, by the following tests in animals. Thus, for example, oral 
administration of a compound of the invention produces ataxia at dosage 
levels of from about 0.1 to about 10 mg/kg, specifically, in rats at about 
3.1 mg/kg, in mice at about 1 mg/kg and in monkeys at about 2.5 mg/kg. 
The compounds of the present invention produce a significant tranquilizing 
effect at a dosage level of from about 0.1 to about 25 mg/kg, specifically 
at a dosage level of about 6.2 mg/kg when administered via the oral route 
to rats in a conflict test procedure [cf. J. R. Vogel, B. Beer, D. Clody, 
Psychopharmacologist, 21, 1 (1970)]. 
In mice, oral administration of from about 0.1 to about 50 mg/kg of a 
compound of the present invention antagonizes the convulsant effects of 
subcutaneously administered pentylenetetrazole and of intraveneously 
administered strychnine. 
Mice treated with from about 0.01 to about 200 mg/kg of a compound of the 
present invention via the oral route increase significantly their food 
consumption. 
The compounds of the present invention in the described dosages may be 
administered orally; however, other routes such as intraperitoneally, 
subcutaneously, intramuscularly or intravenously may be employed. 
The active compounds of the present invention are orally administered, for 
example, with an inert diluent or with an assimilable edible carrier, or 
they may be enclosed in hard or soft gelatin capsules, or they may be 
compressed into tablets, or they may be incorporated directly with the 
food of the diet. For oral therapeutic administration, the active 
compounds of this invention may be incorporated with excipients and used 
in the form of tablets, troches, capsules, elixirs, suspensions, syrups, 
wafers, chewing gum, and the like. Such compositions and preparations 
should contain at least 0.1% of active compound. The percentage in the 
compositions and preparations may, of course, be varied and may 
conveniently be between about 5% to about 75% or more of the weight of the 
unit. The amount of active compound in such therapeutically useful 
compositions or preparations is such that a suitable dosage will be 
obtained. Preferred compositions or preparations according to the present 
invention are prepared so that an oral dosage unit form contains between 
about 10 and 500 milligrams of active compound. 
The tablets, troches, pills, capsules and the like may also contain the 
following: a binder such as gum tragacanth, acacia, corn starch or 
gelatin; an excipient such as dicalcium phosphate; a disintegrating agent 
such as corn starch, potato starch, alginic acid and the like; a lubricant 
such as magnesium stearate; and a sweetening agent such as sucrose, 
lactose or saccharin may be added or a flavoring agent such as peppermint, 
oil of wintergreen, or cherry flavoring. When the dosage unit form is a 
capsule, it may contain in addition to materials of the above type a 
liquid carrier such as a fatty oil. Various other materials may be present 
as coatings or to otherwise modify the physical form of the dosage unit, 
for instance, tablets, pills or capsules may be coated with shellac, sugar 
or both. A syrup or elixir may contain the active compounds, sucrose as a 
sweetening agent, methyl and propyl parabens as preservatives, a dye and a 
flavoring such as cherry or orange flavor. Of course, any material used in 
preparing any dosage unit form should be pharmaceutically pure and 
substantially non-toxic in the amounts employed. 
In the following examples all reactions are run under an inert atmosphere 
(e.g. argon), at room temperature, using anhydrous solvents unless 
otherwise indicated; in addition, reactions which are heated are 
subsequently cooled to room temperature for work-up. In general, solvents 
are evaporated in a rotary flash vacuum apparatus. In this patent 
application, the full name of the parent ring system of compounds 
described as indicated in Column I below is as indicated in Column II. 
______________________________________ 
I II 
______________________________________ 
"4H-s-triazolo[4,3-a][1,5]- 
"5,6-dihydro-4H-s- 
benzodiazepin" triazolo[4,3-a][1,5]- 
benzodiazepin" 
"1H-1,5-benzodiazepin" 
"2,3,4,5-tetrahydro-1H- 
1,5-benzodiazepin" 
"3H-1,5-benzodiazepin" 
"4,5-dihydro-3H-1,5- 
benzodiazepin" 
______________________________________

EXAMPLE 1 
7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione 
A solution of 28.6 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione 
and 23.3 g of phosphorous pentasulfide in 250 ml of pyridine is refluxed, 
with stirring, for 40 minutes under argon. The solvent is evaporated in 
vacuo. 
The residue is stirred in ice water and extracted with methylene chloride. 
The organic phase is washed consecutively with dilute aqueous hydrochloric 
acid, water and dried. The organic phase is filtered through a short 
column of neutral III alumina, the column is washed with ethyl acetate and 
the filtrate evaporated. The residue is triturated with a small amount of 
hot benzene and the product filtered off and dried. 
EXAMPLES 2 - 28 
Following the procedure of Example 1 but substituting the compounds 
indicated in Column I below for 
7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione in Example 1, the 
compounds indicated in Column II are obtained: 
______________________________________ 
I II 
______________________________________ 
2. 5-phenyl-1H-1,5-benzo- 
5-phenyl-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
3. 7-(trifluoromethyl)-5- 
7-(trifluoromethyl)-5- 
phenyl-1H-1,5-benzodia- 
phenyl-1H-1,5-benzodia- 
zepine-2,4-dione zepin-4-one-2-thione 
4. 7-nitro-5-phenyl-1H-1,5- 
7-nitro-5-phenyl-1H- 
benzodiazepine-2,4-dione 
1,5-benzodiazepin-4- 
one-2-thione 
5. 7-methyl-5-phenyl-1H- 
7-methyl-5-phenyl-1H- 
1,5-benzodiazepine- 
1,5-benzodiazepin-4- 
2,4-dione one-2-thione 
6. 7-methoxy-5-phenyl- 
7-methoxy-5-phenyl-1H- 
1H-1,5-benzodia- 1,5-benzodiazepin-4- 
zepine-2,4-dione one-2-thione 
7. 7-(methylthio)-5- 7-(methylthio)-5- 
phenyl-1H-1,5-benzo- 
phenyl-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
8. 7-pentyl-5-phenyl-1H- 
7-pentyl-5-phenyl-1H- 
1,5-benzodiazepine- 
1,5-benzodiazepin-4- 
2,4-dione one-2-thione 
9. 7-pentoxy-5-phenyl- 
7-pentoxy-5-phenyl-1H- 
1H-1,5-benzodiazepine- 
1,5-benzodiazepin-4- 
2,4-dione one-2-thione 
10. 7-bromo-5-phenyl-1H- 
7-bromo-5-phenyl-1H- 
1,5-benzodiazepine- 
1,5-benzodiazepin-4- 
2,4-dione one-2-thione 
11. 7-fluoro-5-phenyl-1H- 
7-fluoro-5-phenyl-1H- 
1,5-benzodiazepine- 
1,5-benzodiazepin-4- 
2,4-dione one-2-thione 
12. 7-cyano-5-phenyl-1H- 
7-cyano-5-phenyl-1H- 
1,5-benzodiazepine- 
1,5-benzodiazepin-4- 
2,4-dione one-2-thione 
13. 7-chloro-5-(2-chloro- 
7-chloro-5-(2-chloro- 
phenyl)-1H-1,5-benzo- 
phenyl)-1H-1,5-benzodia- 
diazepine-2,4-dione 
zepin-4-one-2-thione 
14. 7-chloro-5-(2-fluoro- 
7-chloro-5-(2-fluoro- 
phenyl)-1H-1,5-benzo- 
phenyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
15. 7-chloro-5-(3-chloro- 
7-chloro-5-(3-chloro- 
phenyl)-1H-1,5-benzo- 
phenyl)1H,1,5-benzodia- 
diazepine-2,4-dione 
zepin-4-one-2-thione 
16. 7-chloro-5-(4-chloro- 
7-chloro-5-(4-chloro- 
phenyl)-1H-1,5-benzo- 
phenyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
17. 7-chloro-5-(2-methoxy- 
7-chloro-5-(2-methoxy- 
phenyl)-1H-1,5-benzo- 
phenyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
18. 7-chloro-5-(3-methoxy- 
7-chloro-5-(3-methoxy- 
phenyl)-1H-1,5-benzo- 
phenyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
19. 7-chloro-5-(4-methoxy- 
7-chloro-5-(4-methoxy- 
phenyl)-1H-1,5-benzo- 
phenyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
20. 7-chloro-5-(2-methyl- 
7-chloro-5-(2-methyl- 
phenyl)-1H-1,5-benzo- 
phenyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
21. 7-chloro-5-(3-methyl- 
7-chloro-5-(3-methyl- 
phenyl)-1H-1,5-benzo- 
phenyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
22. 7-chloro-5-(4-methyl- 
7-chloro-5-(4-methyl- 
phenyl)1H-1,5-benzo- 
phenyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
23. 3-methyl-7-chloro-5- 
3-methyl-7-chloro-5- 
phenyl-1H-1,5-benzodia- 
phenyl-1H-1,5-benzodia- 
zepine-2,4-dione zepin-4-one-2-thione 
24. 3-(benzyloxy)-7-chloro- 
3-(benzyloxy)-7-chloro- 
5-phenyl-1H-1,5-benzo- 
5-phenyl-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
25. 3-methoxy-7-chloro-5- 
3-methoxy-7-chloro-5- 
phenyl-1H-1,5-benzo- 
phenyl-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
26. 8-methyl-5-phenyl-1H- 
8-methyl-5-phenyl-1H- 
1,5-benzodiazepine- 
1,5-benzodiazepin-4- 
2,4-dione one-2-thione 
27. 8-chloro-5-phenyl- 
8-chloro-5-phenyl-1H- 
1H-1,5-benzodiazepine- 
1,5-benzodiazepin-4- 
2,4-dione one-2-thione 
28. 8-(trifluoromethyl)-5- 
8-(trifluoromethyl)-5- 
phenyl-1H-1,5-benzodia- 
phenyl-1H-1,5-benzodia- 
zepine-2,4-dione zepin-4-one-2-thione 
______________________________________ 
EXAMPLE 29 
1-Methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]-benzodiazepin-5-one 
Method A 
30.2 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione and 23.8 g 
of acetic acid hydrazide in a mixture of 640 ml n-butanol and 160 ml of 
dimethyl sulfoxide are refluxed with stirring for 24 hours. During this 
time, argon is bubbled through the reaction mixture. The reaction is 
concentrated in vacuo and partitioned between methylene chloride and 
water; the organic phase is washed several times with water, dried and 
filtered through a short Florisil column. After eluting the column with 
ethyl acetate, the combined filtrates are evaporated to give the title 
compound. Recrystallization from ethanol-ethyl acetate, followed by vacuum 
drying at elevated temperatures gives the product. 
Method B 
15.8 g of 2-(methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one and 
8.1 g of acetic acid hydrazide in 400 ml dimethyl formamide are refluxed 
with stirring for 24 hours. During this time nitrogen is bubbled through 
the reaction mixture. The reaction mixture is worked up as described in 
Example 29, Method A, to give the title compound. 
Method C 
A mixture of 6.2 g of 
1-methyl-8-chloro-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one, 5 g of 
copper powder and 2.5 g of potassium acetate in 100 ml bromobenzene are 
refluxed for six hours with stirring. The reaction is diluted with 
methylene chloride, filtered through a short Florisil column and the 
filtrate washed with dilute aqueous ammonium hydroxide. The organic phase 
is washed with water, dried and the solvent evaporated to give the title 
compound. 
Method D 
3.0 g of 2,7-dichloro-5-phenyl-3H-1,5-benzodiazepin-4-one and 1.8 g of 
acetic acid hydrazide in 50 ml of dioxane are refluxed under argon for 24 
hours. 2 ml of water is then added, the reaction stirred for 1 hour and 
the solvent evaporated. The residue is taken up in methylene chloride, 
washed with dilute aqueous sodium bicarbonate, with water and dried. The 
solvent is evaporated and the residue is chromatographed on ten-1000.mu. 
silica gel thick layer plates (20 .times. 20 cm) with ethyl 
acetate-ethanol (9:1) as eluant. The main band, having an approximate Rf 
range of 0.12-0.28, is removed, stirred with acetone-methanol (9:1) and 
the silica gel filtered off. The filtrate is evaporated to give the title 
compound. 
Method E 
Following the procedure of Example 29, Method B, but substituting 15 g of 
2-methoxy-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one for 15.8 g of 
2-(methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one in Example 29, 
Method B, the title compound is obtained. 
Method F 
15 g of acetic acid 2-(7-chloro-5-phenyl-3H-1,5 
-benzodiazepin-4-one-2-yl)hydrazide in 100 ml dimethyl formamide are 
refluxed for 24 hours under a Soxhlet extractor containing 4A molecular 
sieves, under argon. The solvent is evaporated and the crude product is 
purified as described in Example 29, Method D. 
Method G 
3.01 g of 2-hydrazino-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one in 15 ml 
of acetic anhydride is refluxed for 24 hours. The acetic anhydride is 
evaporated and the residual crude product taken up in methylene chloride 
and purified as described in Example 29, Method D. 
Method H 
4.0 g of 
2-[2-(t-butoxycarbonyl)hydrazino]-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4 
-one in 60 ml of n-butyl acetate which contains 2.0 g of hydrogen bromide 
is stirred at room temperature for 1 hour and refluxed for 24 hours. The 
reaction is evaporated, the product dissolved in methylene chloride and 
purified as described in Example 29, Method D. 
Method I 
To 4.96 g of 1-methyl-8-chloro-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one 
in a mixture of 70 ml ethanol and 200 ml of 0.1 N aqueous potassium 
hydroxide is added 7.2 g of diphenyliodonium bromide. The reaction is 
refluxed for 8 hours. The iodobenzene is removed by steam distillation. 
The distillation residue is cooled and partitioned between methylene 
chloride and water. The organic phase is dried and evaporated to give the 
title compound. 
EXAMPLES 30-55 
Following the procedure of Example 29, Method A, but substituting the 
compounds indicated in Column I below for 
7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in Example 29, 
Method A, the compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
30. 5-phenyl-1H-1,5-benzo- 
1-methyl-6-phenyl-4H-s- 
diazepin-4-one-2-thione 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
31. 7-(trifluoro-methyl)-5- 
1-methyl-8-(trifluoro- 
phenyl-1H-1,5-benzodia- 
methyl)-6-phenyl-4H-s- 
zepin-4-one-2-thione 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
32. 7-nitro-5-phenyl-1H 
1-methyl-8-nitro-6- 
1,5-benzodiazepin-4- 
phenyl-4H-s-triazolo- 
one-2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
33. 7-methyl-5-phenyl- 
1-methyl-8-methyl-6- 
1H-1,5-benzodiazepin- 
phenyl-4H-s-triazolo- 
4-one-2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
34. 7-methoxy-5-phenyl- 
1-methyl-8-methoxy- 
1H-1,5-benzodiazepin- 
6-phenyl-4H-s-triazolo- 
4-one-2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
35. 7-(methylthio)-5-phenyl- 
1-methyl-8-(methyl- 
1H-1,5-benzodiazepin- 
thio)-6-phenyl-4H- 
4-one-2-thione s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
36. 7-pentyl-5-phenyl-1H- 
1-methyl-8-pentyl-6- 
1,5-benzodiazepin-4-one- 
phenyl-4H-s-triazolo- 
2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
37. 7-pentoxy-5-phenyl-1H- 
1-methyl-8-pentoxy-6- 
1,5-benzodiazepin-4- 
phenyl-4H-s-triazolo- 
one-2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
38. 7-bromo-5-phenyl-1H- 
1-methyl-8-bromo-6- 
1,5-benzodiazepin-4- 
phenyl-4H-s-triazolo- 
one-2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
39. 7-fluoro-5-phenyl-1H- 
1-methyl-8-fluoro-6- 
1,5-benzodiazepin-4- 
phenyl-4H-s-triazolo- 
one-2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
40. 7-cyano-5-phenyl-1H- 
1-methyl-8-cyano-6- 
1,5-benzodiazepin-4- 
phenyl-4H-s-triazolo- 
one-2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
41. 7-chloro-5-(2-chloro- 
1-methyl-8-chloro-6- 
phenyl)-1H-1,5-benzo- 
(2-chlorophenyl)-4H-s- 
diazepin-4-one-2-thione 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
42. 7-chloro-5-(2-fluoro- 
1-methyl-8-chloro-6- 
phenyl)-1H-1,5-benzo- 
(2-fluorophenyl)-4H- 
diazepin-4-one-2-thione 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
43. 7-chloro-5-(3-chloro- 
1-methyl-8-chloro-6- 
phenyl)-1H-1,5-benzo- 
(3-chlorophenyl)-4H- 
diazepin-4-one-2-thione 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
44. 7-chloro-5-(4-chloro- 
1-methyl-8-chloro-6- 
phenyl)-1H-1,5-benzo- 
(4-chlorophenyl)-4H-s- 
diazepin-4-one-2-thione 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
45. 7-chloro-5-(2-methoxy- 
1-methyl-8-chloro-6- 
phenyl)-1H-1,5-benzo- 
(2-methoxyphenyl)-4H- 
diazepin-4-one-2-thione 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
46. 7-chloro-5-(3-methoxy- 
1-methyl-8-chloro-6- 
phenyl)-1H-1,5-benzo- 
(3-methoxyphenyl)-4H- 
diazepin-4-one-2-thione 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
47. 7-chloro-5-(2-methyl- 
1-methyl-8-chloro-6- 
phenyl)-1H-1,5-benzo- 
(2-methylphenyl)-4H- 
diazepin-4-one-2-thione 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
48. 7-chloro-5-(3-methyl- 
1-methyl-8-chloro-6- 
phenyl)-1H-1,5-benzo- 
(3-methylphenyl)-4H- 
diazepin-4-one-2-thione 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
49. 7-chloro-5-(4-methyl- 
1-methyl-8-chloro-6- 
phenyl)-1H-1,5-benzo- 
(4-methylphenyl)-4H- 
diazepin-4-one-2-thione 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
50. 3-methyl-7-chloro-5- 
1,4-dimethyl-8-chloro- 
phenyl-1H-1,5-benzo- 
6-phenyl-4H-s-triazolo- 
diazepin-4-one-2-thione 
[4,3-a][1,5]benzodia- 
zepin-5-one 
51. 3-(benzyloxy)-7-chloro- 
4-(benzyloxy)-1-methyl-8- 
5-phenyl-1H-1,5-benzodia- 
chloro-6-phenyl-4H-s- 
zepin-4-one-2-thione 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
52. 3-methoxy-7-chloro-5- 
4-(methoxy)-1-methyl-8- 
phenyl-1H-1,5-benzo- 
chloro-6-phenyl-4H-s- 
diazepin-4-one-2-thione 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
53. 8-methyl-5-phenyl-1H- 
1,9-dimethyl-6-phenyl- 
1,5-benzodiazepin-4- 
4H-s-triazolo[4,3-a]- 
one-2-thione [1,5]benzodiazepin-5- 
one 
54. 8-chloro-5-phenyl-1H- 
9-chloro-1-methyl-6- 
1,5-benzodiazepin-4- 
phenyl-4H-s-triazolo- 
one-2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
55. 8-(trifluoromethyl)-5- 
9-(trifluoromethyl)- 
phenyl-1H-1,5-benzo- 
1-methyl-6-phenyl-4H- 
diazepin-4-one-2- s-triazolo[4,3-a][1,5]- 
thione benzodiazepin-5-one 
______________________________________ 
EXAMPLES 56 - 64 
Following the procedure of Example 29, Method A, but substituting the acid 
hydrazides indicated in Column I below for acetic acid hydrazide in 
Example 29, Method A, the compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
56. formic acid hydrazide 
8-chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
57. propionic acid hydrazide 
1-ethyl-8-chloro-6- 
phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodiaze- 
pin-5-one 
58. valeric acid hydrazide 
1-butyl-8-chloro-6- 
phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
59. cyclopropane carboxylic 
1-cyclopropyl-8-chloro- 
acid hydrazide 6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
60. cyclopentane carboxylic 
1-cyclopentyl-8-chloro- 
acid hydrazide 6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
61. phenylacetic acid 1-benzyl-8-chloro- 
hydrazide 6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
62. 2-methyl-propionic 
1-isopropyl-8-chloro- 
acid hydrazide 6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
63. 1-cyanoacetic acid 
1-cyanomethyl-8-chloro- 
hydrazide 6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
64. benzoic acid hydrazide 
1-phenyl-8-chloro- 
6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
______________________________________ 
EXAMPLES 65 - 91 
Following the procedure of Example 29, Method A, but substituting formic 
acid hydrazide for acetic acid hydrazide in Example 29, Method A, and the 
compounds indicated in Column I below for 
7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in Example 29, 
Method A, the compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
65. 5-phenyl-1H-1,5-benzodia- 
6-phenyl-4H- 
zepin-4-one-2-thione 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
66. 7-(trifluoromethyl-5- 
8-(trifluoro- 
phenyl-1H-1,5-benzodia- 
methyl)-6-phenyl-4H-s- 
zepin-4-one-2-thione 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
67. 7-nitro-5-phenyl-1H- 
8-nitro-6-phenyl-4H- 
1,5-benzodiazepin-4- 
s-triazolo-[4,3-a][1,5]- 
one-2-thione benzodiazepin-5-one 
68. 7-methyl-5-phenyl-1H- 
8-methyl-6-phenyl-4H- 
1,5-benzodiazepin-4- 
s-triazolo[4,3-a][1,5]- 
one-2-thione benzodiazepin-5-one 
69. 7-methoxy-5-phenyl-1H- 
8-methoxy-6-phenyl-4H- 
1,5-benzodiazepin-4- 
s-triazolo[4,3-a][1,5]- 
one-2-thione benzodiazepin-5-one 
70. 7-(methylthio)-5-phenyl- 
8-(methylthio)-6-phenyl- 
1H-1,5-benzodiazepin- 
4H-s-triazolo[4,3-a][1,5]- 
4-one-2-thione benzodiazepin-5-one 
71. 7-pentyl-5-phenyl-1H- 
8-pentyl-6-phenyl-4H- 
1,5-benzodiazepin-4- 
s-triazolo[4,3-a][1,5]- 
one-2-thione benzodiazepin-5-one 
72. 7-pentoxy-5-phenyl-1H- 
8-pentoxy-6-phenyl-4H- 
1,5-benzodiazepin-4- 
s-triazolo[4,3-a][1,5]- 
one-2-thione benzodiazepin-5-one 
73. 7-bromo-5-phenyl-1H- 
8-bromo-6-phenyl-4H- 
1,5-benzodiazepin-4- 
s-triazolo[4,3-a][1,5]- 
one-2-thione benzodiazepin-5-one 
74. 7-fluoro-5-phenyl-1H- 
8-fluoro-6-phenyl-4H- 
1,5-benzodiazepin-4- 
s-triazolo[4,3-a][1,5]- 
one-2-thione benzodiazepin-5-one 
75. 7-cyano-5-phenyl-1H- 
8-cyano-6-phenyl-4H- 
1,5-benzodiazepin-4- 
s-triazolo[4,3-a][1,5]- 
one-2-thione benzodiazepin-5-one 
76. 7-chloro-5-(2-chloro- 
8-chloro-6-(2-chloro- 
phenyl)-1H-1,5-benzo- 
phenyl)-4H-s-triazolo- 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
77. 7-chloro-5-(2-fluoro- 
8-chloro-6-(2-fluoro- 
phenyl)-1H-1,5-benzo- 
phenyl)-4H-s-triazolo- 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
78. 7-chloro-5-(3-chloro- 
8-chloro-6-(3-chloro- 
phenyl)-1H-1,5-benzo- 
phenyl)-4H-s-triazolo- 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
79. 7-chloro-5-(4-chloro- 
8-chloro-6-(4-chloro- 
phenyl)-1H-1,5-benzo- 
phenyl)-4H-s-triazolo- 
diazepin-4-pne-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
80. 7-chloro-5-(2-methoxy- 
8-chloro-6-(2-methoxy- 
phenyl)-1H-1,5-benzo- 
phenyl)-4H-s-triazolo- 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
81. 7-chloro-5-(3-methoxy- 
8-chloro-6-(3-methoxy- 
phenyl-1H-1,5-benzo- 
phenyl)-4H-s-triazolo- 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
82. 7-chloro-5-(4-methoxy- 
8-chloro-6-(4-methoxy- 
phenyl)-1H-1,5-benzo- 
phenyl)-4H-s-triazolo- 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
83. 7-chloro-5-(2-methyl- 
8-chloro-6-(2-methyl- 
phenyl)-1H-1,5-benzo- 
phenyl)-4H-s-triazolo- 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
84. 7-chloro-5-(3-methyl- 
8-chloro-6-(3-methyl- 
phenyl)-1H-1,5-benzo- 
phenyl)-4H-s-triazolo- 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
85. 7-chloro-5-(4-methyl- 
8-chloro-6-(4-methyl- 
phenyl)-1H-1,5-benzo- 
phenyl-4H-s-triazolo- 
diazepin-4-one-2-thione 
[4,3-a][1,5]benzodia- 
zepin-5-one 
86. 3-methyl-7-chloro-5- 
4-methyl-8-chloro-6- 
phenyl-1H-1,5-benzo- 
phenyl-4H-s-triazolo- 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
87. 3-(benzyloxy)-7-chloro- 
4-(benzyloxy)-8-chloro- 
5-phenyl-1H-1,5-benzo- 
6-phenyl-4H-s-triazolo 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
88. 3-methoxy-7-chloro- 
4-methoxy-8-chloro-6- 
5-phenyl-1H-1,5-benzo- 
phenyl-4H-s-triazolo- 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
89. 8-methyl-5-phenyl-1H- 
9-methyl-6-phenyl-4H- 
1,5-benzodiazepin-4-one- 
s-triazolo[4,3-a][1,5]- 
2-thione benzodiazepin-5-one 
90. 8-chloro-5-phenyl-1H- 
9-chloro-6-phenyl-4H- 
1,5-benzodiazepin-4- 
s-triazolo[4,3-a][1,5]- 
one-2-thione benzodiazepin-5-one 
91. 8-(trifluoromethyl)- 
9-(trifluoromethyl)-6- 
5-phenyl-1H-1,5-benzo- 
phenyl-4H-s-triazolo- 
diazepin-4-one-2- [4,3-a][1,5]benzodia- 
thione zepin-5-one 
______________________________________ 
EXAMPLE 92 
2-(Methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one 
To 3.03 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in a 
solution of 0.40 g sodium hydroxide and 15 ml of methanol is added, with 
stirring a solution of 1.39 g of methyl iodide in 5 ml of methanol. 
Stirring is continued for 1 hour, the reaction is evaporated, diluted with 
30 ml methylene chloride and filtered through a short Florisil column. 
After washing the column with ethyl acetate, the combined filtrates are 
evaporated to give the title compound. 
EXAMPLES 93 - 96 
Following the procedure of Example 92 but substituting the compounds 
indicated in column I below for methyl iodide and the compounds indicated 
in column II for 7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in 
Example 92, the benzodiazepinones indicated in column III are obtained. 
__________________________________________________________________________ 
I II III 
__________________________________________________________________________ 
benzylbromide 
7-(trifluoromethyl)-5-phenyl- 
2-(benzylthio)-7-(trifluoromethyl)- 
1H-1,5-benzodiazepin-4-one- 
5-phenyl-3H-1,5-benzodiazepin- 
2-thione 4-one 
O-propyl p-toluene- 
7-nitro-5-(o-chlorophenyl)- 
2-(propylthio)-7-nitro-5-(o- 
sulfonate 1H-1,5-benzodiazepin-4-one- 
chlorophenyl)-3H-1,5-benzodia- 
2-thione zepin-4-one 
methyl iodide 
7-(trifluoromethyl)-5-phenyl- 
2-(methylthio)-7-(trifluoromethyl)- 
1H-1,5-benzodiazepin-4-one- 
5-phenyl-3H-1,5-benzodiazepin- 
2-thione 4-one 
dimethyl sulfate 
7-chloro-5-benzyl-1H-1,5- 
2-(methylthio)-7-chloro- 
benzodiazepin-4-one-2-thione 
5-benzyl-3H-1,5-benzodiazepin- 
4-one 
__________________________________________________________________________ 
EXAMPLES 97 - 102 
Following the procedure of Example 92 but substituting the compounds 
indicated in Column I below for 
7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in Example 92, the 
compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
97. 5-phenyl-1H-1,5- 2-(methylthio)-5-phenyl- 
benzodiazepin-4-one- 
3H-1,5-benzodiazepin- 
2-thione 4-one 
98. 7-(trifluoromethyl)-5- 
2-(methylthio)-7-(tri- 
phenyl-1H-1,5-benzo- 
fluoromethyl)-5-phenyl- 
diazepin-4-one-2- 
3H-1,5-benzodiazepin- 
thione 4-one 
99. 7-nitro-5-phenyl- 
2-(methylthio)-7-nitro- 
1H-1,5-benzodiaze- 
5-phenyl-3H-1,5-benzo- 
pin-4-one-2-thione 
diazepin-4-one 
100. 7-methyl-5-phenyl-1H- 
2-(methylthio)-7-methyl- 
1,5-benzodiazepin-4- 
5-phenyl-3H-1,5-benzo- 
one-2-thione diazepin-4-one 
101. 7-methoxy-5-phenyl- 
2-(methylthio)-7-methoxy- 
1H-1,5-benzodiazepin- 
5-phenyl-3H-1,5-benzo- 
4-one-2-thione diazepin-4-one 
102. 7-(methylthio)-5- 
2-(methylthio)-7-(methyl- 
phenyl-1H-1,5-benzo- 
thio)-5-phenyl-3H-1,5- 
diazepin-4-one-2- 
benzodiazepin-4-one 
thione 
______________________________________ 
EXAMPLES 103 - 109 
Following the procedure of Example 29, Method B, but substituting the 
compounds indicated in Column I below for acetic acid hydrazide in Example 
29, Method B, the compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
103. N,N-dimethylglycine- 
1-[(Dimethylamino)- 
hydrazide methyl]-8-chloro-6- 
phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
104. N,N-diethylglycine- 
1-[(Diethylamino)- 
hydrazide methyl]-8-chloro-6- 
phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
105. Pyrrolidinoacetic 
1-[(1-Pyrrolidino)- 
acid hydrazide methyl]-8-chloro-6- 
phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
106. 4-Morpholinoacetic 
1-(4-Morpholinomethyl)- 
acid hydrazide 8-chloro-6-phenyl-4H- 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
107. 1-Piperidinoacetic acid 
1-(1-Piperidinomethyl)- 
hydrazide 8-chloro-6-phenyl-4H- 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
108. N-Methylglycine 1-[(Methylamino)-methyl]- 
hydrazide 8-chloro-6-phenyl-4H- 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
109. 2-(p-Methoxybenzyloxy) 
1-[(p-Methoxybenzyloxy)- 
acetic acid hydrazide 
methyl]-8-chloro-6- 
phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
______________________________________ 
EXAMPLES 110 - 115 
Following the procedure of Example 29, Method B, but substituting the 
compounds indicated in Column I below for acetic acid hydrazide and the 
compounds indicated in Column II below for 
2-(methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one in Example 29, 
Method B, the compounds indicated in Column III are obtained. 
__________________________________________________________________________ 
I II III 
__________________________________________________________________________ 
110. 
formic acid hydrazide 
2-(methylthio)-7-chloro-5- 
8-chloro-6-benzyl-4H-s-triazolo- 
benzyl-3H-1,5-benzodia- 
[4,3-a][1,5]benzodiazepin-5- 
zepin-4-one one 
111. 
acetic acid hydrazide 
2-(methylthio)-7-chloro-5- 
1-methyl-8-chloro-6-benzyl-4H-s- 
benzyl-3H-1,5-benzodia- 
triazolo[4,3-a][1,5]benzodiazepin- 
zepin-4-one 5-one 
112. 
acetic acid hydrazide 
2-(benzylthio)-7-(trifluoro- 
1-methyl-8-(trifluoromethyl)-6- 
methyl)-5-phenyl-3H-1,5- 
phenyl-4H-s-triazolo[4,3-a][1,5]- 
benzodiazepin-4-one 
benzodiazepin-5-one 
113. 
acetic acid hydrazide 
2-(propylthio)-7-nitro-5- 
1-methyl-8-nitro-6-(o-chloro- 
(o-chlorophenyl)-3H-1,5- 
phenyl)-4H-s-triazolo[4,3-a] - 
benzodiazepin-4-one 
[1,5]benzodiazepin-5-one 
114. 
acetic acid hydrazide 
2-(methylthio)-7-(trifluoro- 
1-methyl-8-(trifluoromethyl)-6- 
methyl)-5-phenyl-3H-1,5- 
phenyl-4H-s-triazolo[4,3-a]- 
benzodiazepin-4-one 
[1,5]benzodiazepin-5-one 
115. 
acetic acid hydrazide 
2-(methylthio)-7-(trifluoromethyl)- 
1-methyl-8-(trifluoromethyl)-6- 
5-benzyl-3H-1,5-benzodiazepin- 
benzyl-4H-s-triazolo[4,3-a][1,5]- 
4-one benzodiazepin-5-one 
__________________________________________________________________________ 
EXAMPLES 116 - 121 
Following the procedure of Example 29, Method B, but substituting the 
compounds indicated in Column I below for 
2-(methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one in Example 29, 
Method B, the compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
116. 2-(methylthio)-5-phenyl 
1-methyl-6-phenyl-4H-s- 
3H-1,5-benzodiazepin-4- 
triazolo[4,3-a][1,5]- 
one benzodiazepin-5-one 
117. 2-(methylthio)-7-(tri- 
1-methyl-8-(trifluoromethyl)- 
fluoromethyl)-5-phenyl- 
6-phenyl-4H-s-triazolo- 
3H-1,5-benzodiazepin- 
[4,3-a][1,5]benzodiazepin- 
4-one 5-one 
118. 2-(methylthio)-7-nitro- 
1-methyl-8-nitro-6-phenyl- 
5-phenyl-3H-1,5-ben- 
4H-s-triazolo[4,3-a][1,5]- 
zodiazepin-4-one benzodiazepin-5-one 
119. 2-(methylthio)-7-methyl- 
1-methyl-8-methyl-6-phenyl- 
5-phenyl-3H-1,5-ben- 
4H-s-triazolo[4,3-a][1,5]- 
zodiazepin-4-one benzodiazepin-5-one 
120. 2-(methylthio)-7-methoxy- 
1-methyl-8-methoxy-6-phenyl- 
5-phenyl-3H-1,5-ben- 
4H-s-triazolo[4,3-a][1,5]- 
zodiazepin-4-one benzodiazepin-5-one 
121. 2-(methylthio)-7-(methyl- 
1-methyl-8-(methylthio)-6- 
thio)-5-phenyl-3H-1,5- 
phenyl-4H-s-triazolo[4,3-a]- 
benzodiazepin-4-one 
[1,5]benzodiazepin-5- 
one 
______________________________________ 
Example 122 
1-(Hydroxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin- 
5-one 
3.1 g of 
1-[(p-methoxybenzyloxy)-methyl]-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5 
]benzodiazepin-5-one in 30 ml acetic acid, at 25.degree., is stirred with 
24 ml 48% aqueous hydrobromic acid for 20 minutes. The reaction is 
neutralized with 30% aqueous sodium hydroxide and extracted with 
chloroform. The organic phase is separated, washed with water, dried and 
the solvent evaporated to give the title compound. 
Example 123 
1-(hydroxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin- 
5-one, methanesulfonate 
3.4 g of 
1-(hydroxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin 
-5-one in 30 ml chloroform is reacted with 3.03 g triethylamine and then 
3.44 g methanesulfonyl chloride. The reaction is stirred at 20.degree. for 
90 minutes, washed with water, then with saturated aqueous sodium chloride 
and dried. The solvent is evaporated to give the title compound. 
EXAMPLE 124 
1-(Diethylaminomethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiaz 
epin-5-one 
3.35 g of 
1-(Hydroxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin 
-5-one, methanesulfonate in 15 ml dimethylsulfoxide at 0.degree. is added 
dropwise with stirring to 3 ml of diethylamine in 10 ml dimethylsulfoxide. 
The reaction is stirred at 20.degree. for 2 hours, diluted with methylene 
chloride, washed with water and then saturated aqueous sodium chloride. 
After drying, the solvent is evaporated to give the title compound. 
EXAMPLES 125 - 132 
Following the procedure of Example 124, but substituting the amines 
indicated in Column I below for diethylamine amine in Example 124, the 
compounds in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
125. ammonia 1-(aminomethyl)-8-chloro- 
6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
126. methylamine 1-(methylaminomethyl)- 
8-chloro-6-phenyl-4H- 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
127. dimethylamine 
1-(dimethylaminomethyl)- 
8-chloro-6-phenyl-4H- 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
128. pyrrolidine 1-[(1-pyrrolidino)- 
methyl]-8-chloro-6- 
phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
129. morpholine 1-(4-morpholinomethyl)- 
8-chloro-6-phenyl-4H- 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
130. 2-ethanolamine 
1-[[(2-hydroxyethyl)- 
amino]-methyl]-8- 
chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
131. piperidine 1-(piperidinomethyl)- 
8-chloro-6-phenyl-4H- 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
132. benzylamine 1-[(benzylamino)-methyl]- 
8-chloro-6-phenyl-4H- 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
______________________________________ 
EXAMPLE 133 
2-Methoxy-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one 
To 11.4 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione stirred in 
150 ml methanol is added, dropwise, approximately 2.1 g of diazomethane in 
ether. After addition is complete, the reaction is stirred for 1 hour and 
filtered. The filtrate is evaporated and the residue diluted with a small 
amount of ether. The suspension is filtered and the filtrate evaporated to 
give the title compound. 
EXAMPLE 134 
1-[[(Benzyloxycarbonyl)-amino]-methyl]-8-chloro-6-phenyl-4H-s-triazolo[4,3- 
a][1,5]benzodiazepin-5-one 
9.0 g of 2-methoxy-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one and 6.69 g 
of 1-[(benzyloxycarbonyl)amino]acetic acid hydrazide in 210 ml n-butanol 
and 50 ml dimethyl sulfoxide are heated at 140.degree. for 9 hours. The 
reaction is evaporated and the residue is worked up as described in 
Example 29, Method D, to give the title compound. 
EXAMPLE 135 
1-(Aminomethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a]-[1,5]benzodiazepin-5 
-one 
4.5 g of 
1-[[(benzyloxycarbonyl)amino]-methyl]-8-chloro-6-phenyl-4H-s-triazolo[4,3- 
a][1,5]benzodiazepin-5-one in 60 ml acetic acid saturated with hydrogen 
bromide is stirred at 20.degree. for 1 hour. The reaction mixture is 
concentrated to one-half its original volume in vacuo and diluted with 
ether. The precipitate is filtered off, suspended in methylene chloride 
and shaken with excess 2N aqueous sodium bicarbonate. The organic phase is 
separated, washed with water, dried and evaporated to give the title 
compound. 
EXAMPLE 136 
1-(Acetoxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin- 
5-one 
3.4 g of 
1-(hydroxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin 
-5-one and 1.0 g of acetic anhydride in 10 ml of pyridine are warmed in a 
steam bath for 0.2 hour and stirred at room temperature for 10 hours. The 
reaction mixture is cooled, diluted with 100 ml methylene chloride and 
washed with 100 ml water containing 0.84 g sodium bicarbonate. The organic 
phase is washed four times with water, dried and evaporated. The residue 
is triturated with a minimum amount of ether and the title compound 
filtered off, dried and recrystallized from methylene chloride and ether. 
Example 137 
4-Acetoxy-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one 
6.2 g of 8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one, 3 
g of N-chlorosuccinimide and 0.1 g of azodiisobutyronitrile in 200 ml 
benzene are refluxed for 1 hour. The solvent is evaporated and the residue 
(which contains 
4,8-dichloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one) is 
heated on a steam-bath for 10 minutes with 90 g of glacial acetic acid and 
2.5 g of sodium acetate. The reaction is evaporated and the residue 
partitioned between chloroform and dilute aqueous sodium bicarbonate. The 
chloroform is washed with water, dried and the solvent evaporated to give 
the title compound. 
EXAMPLE 138 
4-Ethoxy-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one 
Following the procedure of Example 137 but substituting ethanol for both 
the glacial acetic acid and the sodium acetate in Example 137. the title 
compound is obtained. 
EXAMPLE 139 
4-Hydroxy-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one 
3.5 g of 
4-acetoxy-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one 
and 2.8 ml of 4N aqueous sodium hydroxide in 160 ml of ethanol are stirred 
overnight at 25.degree.. The reaction is neutralized with 0.5 g of acetic 
acid and the solvent is evaporated. The residue is partitioned between 
chloroform and water, the organic phase is dried and the solvent 
evaporated to give the title compound. 
EXAMPLE 140 
7-Chloro-5-benzyl-1H-1,5-benzodiazepine-2,4-dione 
Method A 
To a stirred refluxing solution of 22.3 g of 2-benzylamino-4-chloroaniline 
in 400 ml benzene is added, dropwise, a solution of 13.8 g of malonyl 
dichloride in 45 ml benzene. After addition is complete the reaction was 
refluxed for 7 hours, concentrated to 1/2 the original volume and cooled. 
The title compound is filtered off and dried. The filtrate is evaporated 
and the residue recrystallized from a mixture of ethanol-dimethylformamide 
to give additional product. 
Method B 
9.2 g of N-benzyl-N-(2'-amino-5'-chloro-phenyl)-malonamic acid, ethyl ester 
is added to a solution of 0.73 g of sodium in 100 ml ethanol. After 
refluxing for 2 hours the reaction is evaporated, the residue dissolved in 
water and acidified with hydroacetic acid. The title compound is filtered 
off and dried. 
Method C 
30 g of N-benzyl-N-(2'-nitro-5'-chloro-phenyl)-malonamic acid ethyl ester 
is added to a stirred suspension of 59 g iron powder, 360 ml of ethanol, 
150 ml acetic acid and 105 ml water at reflux. After two hours, the 
reaction is filtered and the filtrate evaporated. The residue is treated 
with dilute aqueous ammonium hydroxide, extracted with methylene chloride, 
washed with water and dried. The solvent is evaporated and the residue 
treated with ethanolic potassium hydroxide. The ethanol is evaporated, the 
residue taken up in water and acidified to pH 6 with hydrochloric acid. 
The title compound is filtered off and dried. 
Method D 
11 g of N-benzyl-N-(2'-amino-5'-chloro-phenyl)-malonamic acid ethyl ester 
in 50 ml ethanol containing 1.7 g potassium hydroxide is kept at room 
temperature for 6 hours, refluxed for 45 minutes and the solvent 
evaporated. The residue is taken up in water, neutralized to pH 7 with 
hydrochloric acid and the title compound filtered off and dried. 
EXAMPLES 141 - 151 
Following the procedure of Example 140, Method A, but substituting the 
compounds indicated in Column I below for 2-benzylamino-4-chloroaniline in 
Example 140, Method A, the compounds in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
141. 2-benzylamino-4- 7-(trifluoromethyl)-5- 
(trifluoromethyl)aniline 
benzyl-1H-1,5-benzodia- 
zepine-2,4-dione 
142. 2-benzylamino-4- 7-methyl-5-benzyl-1H- 
methylaniline 1,5-benzodiazepine- 
2,4-dione 
143. 2-benzylamino-aniline 
5-benzyl-1H-1,5-benzo- 
diazepine-2,4-dione 
144. 2-benzylamino-4- 7-methoxy-5-benzyl-1H- 
methoxyaniline 1,5-benzodiazepine- 
2,4-dione 
145. 2-benzylamino-5- 8-chloro-5-benzyl-1H- 
chloroaniline 1,5-benzodiazepine- 
2,4-dione 
146. 2-benzylamino-5- 8-(trifluoromethyl)-5- 
(trifluoromethyl)aniline 
benzyl-1H-1,5-benzo- 
diazepine-2,4-dione 
147. 2-(p-methoxybenzyl- 
7-chloro-5-(p-methoxy- 
amino)-4-chloroaniline 
benzyl)-1H-1,5-benzodia- 
zepine-2,4-dione 
148. 2-(p-methoxybenzyl- 
7-nitro-5-(p-methoxy- 
amino)-4-nitroaniline 
benzyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
149. 2-(p-methoxybenzyl- 
7-methoxy-5-(p-methoxy- 
amino)-4-methoxy- benzyl)-1H-1,5-benzo- 
aniline diazepine-2,4-dione 
150. 2-(p-methoxypenzyl- 
7-methyl-5-(p-methoxy- 
amino)-4-methyl- benzyl)-1H-1,5-benzo- 
aniline diazepine-2,4-dione 
151. 2-(o,p-dimethoxy- 7-(trifluoromethyl)-5- 
benzylamino)-4- (o,p-dimethoxybenzyl)- 
(trifluoromethyl) 1H-1,5-benzodiazepine- 
methylaniline 2,4-dione 
______________________________________ 
EXAMPLES 152-164 
Following the procedure of Example 1 but substituting the compounds 
indicated in Column 1 below for 
7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione in Example 1, the 
compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
152. 5-benzyl-1H-1,5-benzo- 
5-benzyl-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
153. 7-chloro-5-benzyl-1H- 
7-chloro-5-benzyl- 
1,5-benzodiazepine- 
1H-1,5-benzodiazepin- 
2,4-dione 4-one-2-thione 
154. 7-methyl-5-benzyl-1H- 
7-methyl-5-benzyl-1H- 
1,5-benzodiazepine- 
1,5-benzodiazepin-4- 
2,4-dione one-2-thione 
155. 7-methoxy-5-benzyl-1H- 
7-methoxy-5-benzyl-1H- 
1,5-benzodiazepine- 
1,5-benzodiazepin-4- 
2,4-dione one-2-thione 
156. 8-(trifluoromethyl)-5- 
8-(trifluoromethyl)-5- 
benzyl-1H-1,5-benzodia- 
benzyl-1H-1,5-benzo- 
zepine-2,4-dione diazepin-4-one-2-thione 
157. 8-chloro-5-benzyl-1H- 
8-chloro-5-benzyl-1H- 
1,5-benzodiazepine- 
1,5-benzodiazepin-4- 
2,4-dione one-2-thione 
158. 7-(trifluoromethyl)-5- 
7-(trifluoromethyl)-5- 
benzyl-1H-1,5-benzo- 
benzyl-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2-thione 
159. 7-chloro-5-(p-methoxy- 
7-chloro-5-(p-methoxy- 
benzyl)-1H-1,5-benzo- 
benzyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2- 
thione 
160. 7-nitro-5-(p-methoxy- 
7-nitro-5-(p-methoxy- 
benzyl)-1H-1,5-benzo- 
benzyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2- 
thione 
161. 7-methoxy-5-(p-methoxy- 
7-methoxy-5-(p-methoxy- 
benzyl)-1H-1,5-benzo- 
benzyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2- 
thione 
162. 7-methyl-5-(p-methoxy- 
7-methyl-5-(p-methoxy- 
benzyl)-1H-1,5-benzo- 
benzyl)-1H-1,5-benzo- 
diazepine-2,4-dione 
diazepin-4-one-2- 
thione 
163. 7-(trifluoromethyl)-5- 
7-(trifluoromethyl)-5- 
(p-methoxybenzyl)-1H- 
(p-methoxybenzyl)- 
1,5-benzodiazepine-2,4- 
1H-1,5-benzodiazepin- 
dione 4-one-2-thione 
164. 7-(trifluoromethyl)-5- 
7-(trifluoromethyl)-5- 
(o,p-dimethoxybenzyl)- 
(o,p-dimethoxybenzyl)- 
1H-1,5-benzodiazepine- 
1H-1,5-benzodiazepin- 
2,4-dione 4-one-2-thione 
______________________________________ 
Examples 165 - 177 
Following the procedure of Example 29, Method A, but substituting the 
compounds indicated in Column I below for 
7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in Example 29, 
Method A, the compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
165. 5-benzyl-1H-1,5-benzo- 
1-methyl-6-benzyl-4H- 
diazepin-4-one-2-thione 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
166. 7-chloro-5-benzyl-1H- 
1-methyl-8-chloro-6- 
1,5-benzodiazepin-4-one- 
benzyl-4H-s-triazolo- 
2-thione [4,3-2][1,5]benzodia- 
zepin-5-one 
167. 7-methyl-5-benzyl-1H- 
1-methyl-8-methyl-6- 
1,5-benzodiazepin-4- 
benzyl-4H-s-triazolo- 
one-2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
168. 7-methoxy-5-benzyl-1H- 
1-methyl-8-methoxy-6- 
1,5-benzodiazepin-4- 
benzyl-4H-s-triazolo- 
one-2-thione [4,3-2][1,5]benzodia- 
zepin-5-one 
169. 8-(trifluoromethyl)-5- 
1-methyl-9-(trifluoro- 
benzyl-1H-1,5-benzodia- 
methyl)-6-benzyl-4H-s- 
zepin-4-one-2-thione 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
170. 8-chloro-5-benzyl-1H- 
1-methyl-9-chloro-6- 
1,5-benzodiazepin-4- 
benzyl-4H-s-triazolo- 
one-2-thione [4,3-a][1,5]benzo- 
diazepin-5-one 
171. 7-(trifluoromethyl)-5- 
1-methyl-8-(trifluoro- 
benzyl-1H-1,5-benzodia- 
methyl)-6-benzyl-4H-s- 
zepin-4-one-2-thione 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
172. 7-chloro-5-(p-methoxy- 
1-methyl-8-chloro-6- 
benzyl)-1H-1,5-benzo- 
(p-methoxybenzyl)-4H- 
diazepin-4-one-2- s-triazolo[4,3-a][1,5]- 
thione benzodiazepin-5-one 
173. 7-nitro-5-(p-methoxy- 
1-methyl-8-nitro-6- 
benzyl)-1H-1,5-benzo- 
(p-methoxybenzyl)-4H- 
diazepin-4-one-2- s-triazolo[4,3-a][1,5]- 
thione benzodiazepin-5-one 
174. 7-methoxy-5-(p-methoxy- 
1-methyl-8-methoxy-6- 
benzyl)-1H-1,5-benzo- 
(p-methoxybenzyl)-4H- 
diazepin-4-one-2- s-triazolo[4,3-a][1,5]- 
thione benzodiazepin-5-one 
175. 7-methyl-5-(p-methoxy- 
1-methyl-8-methyl-6- 
benzyl)-1H-1,5-benzo- 
(p-methoxybenzyl)-4H- 
diazepin-4-one-2- s-triazolo[4,3-a][1,5]- 
thione benzodiazepin-5-one 
176. 7-(trifluoromethyl)-5- 
1-methyl-8-(trifluoro- 
(p-methoxybenzyl)-1H- 
methyl)-6-(p-methoxy- 
1,5-benzodiazepin-4-one- 
benzyl)-4H-s-triazolo 
2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
177. 7-(trifluoromethyl)-5- 
1-methyl-8-(trifluoro- 
(o,p-dimethoxybenzyl)- 
methyl)-6-(o,p-dimethoxy- 
1H-1,5-benzodiazepin- 
benzyl)-4H-s-triazolo- 
4-one-2-thione [4,3-a][1,5]benzodia- 
zepin-5-one 
______________________________________ 
EXAMPLES 178 - 189 
Following the procedure of Example 29, Method A, but substituting the acid 
hydrazides indicated in Column I below for acetic acid hydrazide and the 
compounds indicated in column II below for 
7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in Example 29, 
Method A, the compounds in Column III are obtained: 
__________________________________________________________________________ 
I II III 
__________________________________________________________________________ 
178. 
formic acid hydrazide 
7-chloro-5-benzyl-1H-1,5-benzo- 
8-chloro-6-benzyl-4H-s-triazolo- 
diazepin-4-one-2-thione 
[4,3-a][1,5]benzodiazepin-5-one 
179. 
propionic acid hydra- 
7-chloro-5-benzyl-1H-1,5-benzo- 
1-ethyl-8-chloro-6-benzyl-4H-s- 
zide diazepin-4-one-2-thione 
triazolo[4,3-a][1,5]benzodia- 
zepin-5-one 
180. 
cyclopropane carboxylic 
7-chloro-5-benzyl-1H-1,5-benzo- 
1-cyclopropyl-8-chloro-6- 
acid hydrazide 
diazepin-4-one-2-thione 
benzyl-4H-s-triazolo[4,3-a]- 
[1,5]benzodiazepin-5-one 
181. 
N,N-dimethyl- 
7-chloro-5-benzyl-1H-1,5-benzo- 
1-[(dimethylamino)methyl]-8- 
aminoglycine hydrazide 
diazepin-4-one-2-thione 
chloro-6-benzyl-4H-s-triazolo- 
[4,3-a][1,5]benzodiazepin-5- 
one 
182. 
formic acid 7-(trifluoromethyl)-5-(p- 
8-(trifluoromethyl)-6-(p-methoxy- 
hydrazide methoxybenzyl)-1H-1,5-benzo- 
benzyl)-4H-s-triazolo[4,3-a]- 
diazepin-4-one-2-thione 
[1,5]benzodiazepin-5-one 
183. 
propionic acid 
7-(trifluoromethyl)-5-(p- 
1-ethyl-8-(trifluoromethyl)-6- 
hydrazide methoxybenzyl)-1H-1,5-benzo- 
(p-methoxybenzyl)-4H-s-triazolo- 
diazepin-4-one-2-thione 
[4,3-a][1,5]benzodiazepin-5-one 
184. 
cyclopropane 7-(trifluoromethyl)-5-(p- 
1-cyclopropyl-8-(trifluoromethyl)- 
carboxylic acid 
methoxybenzyl)-1H-1,5-benzo- 
6-(p-methoxybenzyl)-4H-s- 
hydrazide diazepin-4-one-2-thione 
triazolo[4,3-a][1,5]benzodia- 
zepin-5-one 
185. 
N,N-dimethyl- 
7-(trifluoromethyl)-5-(p- 
1-[(dimethylamino)methyl]-8- 
aminoglycine methoxybenzyl)-1H-1,5-benzo- 
(trifluoromethyl)-6-(p-methoxy- 
hydrazide diazepin-4-one-2-thione 
benzyl)-4H-s-triazolo[4,3-a]- 
[1,5]benzodiazepin-5-one 
186. 
formic acid 7-nitro-5-(p-methoxybenzyl)- 
8-nitro-6-(p-methoxybenzyl)- 
hydrazide 1H-1,5-benzodiazepin-4-one- 
4H-s-triazolo[ 4,3-a][1,5]- 
2-thione benzodiazepin-5-one 
187. 
propionic acid 
7-nitro-5-(p-methoxybenzyl)- 
1-ethyl-8-nitro-6-(p-methoxy- 
hydrazide 1H-1,5-benzodiazepin-4-one- 
benzyl)-4H-s-triazolo[4,3-a]- 
2-thione [1,5]benzodiazepin-5-one 
188. 
cyclopropane 7-nitro-5-(p-methoxybenzyl)- 
1-cyclopropyl-8-nitro-6- 
carboxylic acid 
1H-1,5-benzodiazepin-4-one- 
(p-methoxybenzyl)-4H-s-tria- 
hydrazide 2-thione zolo[4,3-a][1,5]benzodiazepin- 
5-one 
189. 
N,N-dimethyl- 
7-nitro-5-(p-methoxybenzyl)- 
1-[(dimethylamino)methyl]-8- 
aminoglycine 1H-1,5-benzodiazepin-4-one- 
nitro-6-(p-methoxybenzyl)- 
hydrazide 2-thione 4H-s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
__________________________________________________________________________ 
EXAMPLE 190 
8-Chloro-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one 
Method A 
2.92 g of 8-chloro-6-benzyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one in 
300 ml acetic acid containing 0.3 g of pre-reduced Raney nickel catalyst 
is hydrogenated at 60.degree. starting with an initial hydrogen pressure 
of 60 p.s.i. The reduction is stopped after 0.01 mole of hydrogen has been 
absorbed, the catalyst filtered off and the solvent evaporated. The 
residue is stirred with water and the title compound is filtered off and 
dried. 
Method B 
2.92 g of 
8-chloro-6-(p-methoxybenzyl)-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one 
in 100 ml of anhydrous hydrogen fluoride is stirred at 20.degree. C for 
one hour. The hydrogen fluoride is then evaporated; the residue is 
partitioned between methylene chloride and dilute aqueous sodium 
bicarbonate. The organic phase is washed with water, dried and evaporated. 
The residue is stirred with ether and the title compound is filtered off 
and dried. 
EXAMPLES 191 - 201 
Following the procedure of Example 190, Method A, but substituting the 
compounds indicated in Column I below for 
8-chloro-6-benzyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one in Example 
190, Method A, the compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
191. 1-methyl-6-benzyl-4H-s- 
1-methyl-4H-s-triazolo- 
triazolo[4,3-a][1,5]ben- 
[4,3-a][1,5]benzodia- 
zodiazepin-5-one zepin-5-one 
192. 1-methyl-8-chloro-6- 
1-methyl-8-chloro-4H- 
benzyl-4H-s-triazolo- 
s-triazolo [4,3-a][1,5]- 
[4,3-a][1,5]benzodia- 
benzodiazepin-5-one 
zepin-5-one 
193. 1-methyl-8-methyl-6- 
1-methyl-8-methyl-4H- 
benzyl-4H-s-triazolo- 
s-triazolo [4,3-a][1,5]- 
[4,3-a][1,5]benzodia- 
benzodiazepin-5-one 
zepin-5-one 
194. 1-methyl-8-methoxy- 
1-methyl-8-methoxy- 
6-benzyl-4H-s-triazolo- 
4H-s-triazolo [4,3-a]- 
[4,3-a][1,5]benzodia- 
[1,5]benzodiazepin-5- 
zepin-5-one one 
195. 1-methyl-9-(trifluoro- 
1-methyl-9-(trifluoro- 
methyl)-6-benzyl-4H- 
methyl)-4H-s-triazolo- 
s-triazolo[4,3-a]- 
[4,3-a][1,5]benzodia- 
[1,5]benzodiazepin- 
zepin-5-one 
5-one 
196. 1-methyl-9-chloro-6- 
1-methyl-9-chloro- 
benzyl-4H-s-triazolo- 
4H-s-triazolo[4,3-a]- 
[4,3-a][1,5]benzodia- 
[1,5]benzodiazepin- 
zepin-5-one 5-one 
197. 1-methyl-8-(trifluoro- 
1-methyl-8-(trifluoro- 
methyl)-6-benzyl-4H- 
methyl)-4H-s-triazolo- 
s-triazolo[4,3-a]- 
[4,3-a][1,5]benzodia- 
[1,5]benzodiazepin- 
zepin-5-one 
5-one 
198. 8-chloro-6-benzyl-4H- 
8-chloro-4H-s-triazolo- 
s-triazolo[4,3-a][1,5]- 
[4,3-a][1,5]benzodia- 
benzodiazepin-5-one 
zepin-5-one 
199. 1-ethyl-8-chloro-6- 
1-ethyl-8-chloro-4H- 
benzyl-4H-s-triazolo- 
s-triazolo[4,3-a][1,5]- 
[4,3-a][1,5]benzo- 
benzodiazepin-5-one 
diazepin-5-one 
200. 1-cyclopropyl-8-chloro- 
1-cyclopropyl-8-chloro- 
6-benzyl-4H-s-triazolo- 
4H-s-triazolo[4,3-a]- 
[4,3-a][1,5] benzodia- 
[1,5]benzodiazepin-5- 
zepin-5-one one 
201. 1-[(dimethylamino)- 
1-[(dimethylamino)- 
methyl]-8-chloro-6- 
methyl]-8-chloro-4H- 
benzyl-4H-s-triazolo- 
s-triazolo[4,3-a][1,5]- 
[4,3-a][1,5]benzodia- 
benzodiazepin-5-one 
zepin-5-one 
______________________________________ 
Examples 202 - 215 
Following the procedure of Example 190, Method B, but substituting the 
compounds indicated in Column I below for 
8-chloro-6-(p-methoxybenzyl)-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one 
in Examples 190, Method B, the compounds indicated in Column II are 
obtained. 
______________________________________ 
I II 
______________________________________ 
202. 8-(trifluoromethyl)-6- 
8-(trifluoromethyl)-4H- 
(p-methoxybenzyl)-4H- 
s-triazolo[4,3-a][1,5]- 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
benzodiazepin-5-one 
203. 1-ethyl-8-(trifluoro- 
1-ethyl-8-(trifluoro- 
methyl)-6-(p-methoxy- 
methyl)-4H-s-triazolo- 
benzyl)-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
zepin-5-one 
204. 1-cyclopropyl-8-(tri- 
1-cyclopropyl-8-(tri- 
fluoromethyl)-6-(p- 
fluorometyl)-4H-s- 
methoxybenzyl)-4H-s- 
triazolo[4,3-a][1,5]- 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
benzodiazepin-5-one 
205. 1-[(dimethylamino)- 
1-[(dimethylamino)- 
methyl]-8-(trifluoro- 
methyl]-8-(trifluoro- 
methyl)-6-(p-methoxy- 
methyl)-4H-s-triazolo- 
benzyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
zepin-5-one 
206. 8-nitro-6-(p-methoxy- 
8-nitro-4H-s-triazolo- 
benzyl)-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
zepin-5-one 
207. 1-ethyl-8-nitro-6-(p- 
1-ethyl-8-nitro-4H-s- 
methoxybenzyl)-4H-s- 
triazolo[4,3-a][1,5]- 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
benzodiazepin-5-one 
208. 1-cyclopropyl-8-nitro- 
1-cyclopropyl-8-nitro- 
6-(p-methoxybenzyl)- 
4H-s-triazolo[4,3-a]- 
4H-s-triazolo[4,3-a]- 
[1,5]benzodiazepin- 
[1,5]benzodiazepin- 
5-one 
5-one 
209. 1-[(dimethylamino)- 
1-[(dimethylamino)- 
methyl]-8-nitro-6-(p- 
methyl]-8-nitro-4H-s- 
methoxybenzyl)-4H-s- 
triazolo[4,3-a][1,5]- 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
benzodiazepin-5-one 
210. 1-methyl-8-chloro-6- 
1-methyl-8-chloro-4H- 
(p-methoxybenzyl)-4H- 
s-triazolo[4,3-a][1,5]- 
s-triazolo[4,3-a] [1,5]- 
benzodiazepin-5-one 
benzodiazepin-5-one 
211. 1-methyl-8-nitro-6- 
1-methyl-8-nitro-4H- 
(p-methoxybenzyl)-4H- 
s-triazolo[4,3-a][1,5]- 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
benzodiazepin-5-one 
212. 1-methyl-8-methoxy-6- 
1-methyl-8-methoxy- 
(p-methoxybenzyl)-4H- 
4H-s-triazolo[4,3-a]- 
s-triazolo[4,3-a][1,5]- 
[1,5]benzodiazepin-5- 
benzodiazepin-5-one 
one 
213. 1-methyl-8-methyl-6- 
1-methyl-8-methyl- 
(p-methoxybenzyl)-4H- 
4H-s-triazolo[4,3-a]- 
s-triazolo[4,3-a][1,5]- 
[1,5]benzodiazepin-5- 
benzodiazepin-5-one 
one 
214. 1-methyl-8-(trifluoro- 
1-methyl-8-(trifluoro- 
methyl)-6-(p-methoxy- 
methyl)-4H-s-triazolo- 
benzyl)-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
zepin-5-one 
215. 1-methyl-8-(trifluoro- 
1-methyl-8-(trifluoro- 
methyl)-6-(o,p-dimethoxy- 
methyl)-4H-s-triazolo- 
benzyl)-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
[4,3-a][1,5]benzodia- 
zepin-5-one 
zepin-5-one 
______________________________________ 
EXAMPLES 216 - 235 
Following the procedure of Example 29, Methods C or I, but substituting the 
compounds indicated in Column I below for 
1-methyl-8-chloro-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one in Example 
29, Methods C or I, the compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
216. 1-methyl-4H-s-triazolo- 
1-methyl-6-phenyl-4H- 
[4,3-a][1,5]benzodia- 
s-triazolo[4,3-a][1,5]- 
zepin-5-one benzodiazepin-5-one 
217. 1-methyl-8-chloro-4H- 
1-methyl-8-chloro-6- 
s-triazolo[4,3-a][1,5]- 
phenyl-4H-s-triazolo- 
benzodiazepin-5-one 
[4,3-a][1,5]benzodiaze- 
pin-5-one 
218. 1-methyl-8-methoxy-4H- 
1-methyl-8-methoxy-6- 
s-triazolo[4,3-a][1,5]- 
phenyl-4H-s-triazolo- 
benzodiazepin-5-one 
[4,3-a][1,5]benzodia- 
zepin-5-one 
219. 1-methyl-8-(trifluoro- 
1-methyl-8-(trifluoro- 
methyl)-4H-s-triazolo- 
methyl)-6-phenyl-4H- 
[4,3-a][1,5]benzodia- 
s-triazolo[4,3-a][1,5]- 
zepin-5-one benzodiazepin-5-one 
220. 1-methyl-8-nitro-4H- 
1-methyl-8-nitro-6- 
s-triazolo[4,3-a][1,5]- 
phenyl-4H-s-triazolo- 
benzodiazepin-5-one 
[4,3-a][1,5]benzodia- 
zepin-5-one 
221. 1-methyl-9-chloro- 
1-methyl-9-chloro-6- 
4H-s-triazolo[4,3-a]- 
phenyl-4H-s-triazolo- 
[1,5]benzodiazepin-5- 
[4,3-a][1,5]benzodia- 
one zepin-5-one 
222. 1-methyl-9-(trifluoro- 
1-methyl-9-(trifluoro- 
methyl)-4H-s-triazolo- 
methyl)-6-phenyl-4H- 
[4,3-a][1,5]benzodia- 
s-triazolo[4,3-a]- 
zepin-5-one [1,5]benzodiazepin- 
5-one 
223. 1,8-dimethyl-4H-s- 
1,8-dimethyl-6-phenyl- 
triazolo[4,3-a][1,5]- 
4H-s-triazolo[4,3-a]- 
benzodiazepin-5-one 
[1,5]benzodiazepin- 
5-one 
224. 8-(trifluoromethyl)-4H- 
8-(trifluoromethyl)-6- 
s-triazolo[4,3-a][1,5]- 
phenyl-4H-s-triazolo- 
benzodiazepin-5-one 
[4,3-a][1,5]benzodia- 
zepin-5-one 
225. 1-ethyl-8-(trifluoro- 
1-ethyl-8-(trifluoro- 
methyl)-4H-s-triazolo- 
methyl)-6-phenyl-4H- 
[4,3-a][ 1,5]benzodia- 
s-triazolo[4,3-a][1,5]- 
zepin-5-one benzodiazepin-5-one 
226. 1-cyclopropyl-8-(tri- 
1-cyclopropyl-8-(tri- 
fluoromethyl)-4H-s- 
fluoromethyl)-6-phenyl- 
triazolo[4,3-a][1,5]- 
4H-s-triazolo[4,3-a]- 
benzodiazepin-5-one 
[1,5]benzodiazepin- 
5-one 
227. 1-[(dimethylamino)- 
1-[(dimethylamino)- 
methyl]-8-(trifluoro- 
methyl]-8-(trifluoro- 
methyl)-4H-s-triazolo- 
methyl)-6-phenyl-4H- 
[4,3-a][1,5]benzo- 
s-triazolo[4,3-a][1,5]- 
diazepin-5-one benzodiazepin-5-one 
228. 8-nitro-4H-s-triazolo- 
8-nitro-6-phenyl-4H- 
[4,3-a][1,5]benzodia- 
s-triazolo[4,3-a]- 
zepin-5-one [1,5]benzodiazepin- 
5-one 
229. 1-ethyl-8-nitro-4H- 
1-ethyl-8-nitro-6- 
s-triazolo[4,3-a]- 
phenyl-4H-s-triazolo- 
[1,5]benzodiazepin- 
[4,3-a][1,5]benzodia- 
5-one zepin-5-one 
230. 1-cyclopropyl-8-nitro- 
1-cyclopropyl-8-nitro- 
4H-s-triazolo[4,3-a]- 
6-phenyl-4H-s-triazolo- 
[1,5]benzodiazepin-5- 
[4,3-a][1,5]benzodia- 
one zepin-5-one 
231. 1-[(dimethylamino)- 
1-[(dimethylamino)- 
methyl]-8-nitro-4H- 
methyl]-8-nitro-6- 
s-triazolo[4,3-a]- 
phenyl-4H-s-triazolo- 
[1,5]benzodiazepin- 
[4,3-a][1,5]benzodia- 
5-one zepin-5-one 
232. 8-chloro-4H-s-tria- 
8-chloro-6-phenyl-4H- 
zolo[4,3-a][1,5]- 
s-triazolo[4,3-a]- 
benzodiazepin-5-one 
[1,5]benzodiazepin-5- 
one 
233. 1-ethyl-8-chloro-4H- 
1-ethyl-8-chloro-6- 
s-triazolo[4,3-a]- 
phenyl-4H-s-triazolo- 
[1,5]benzodiazepin- 
[4,3-a][1,5]benzodia- 
5-one zepin-5-one 
234. 1-cyclopropyl-8- 1-cyclopropyl-8-chloro- 
chloro-4H-s-triazolo- 
6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodia- 
[ 4,3-a][1,5]benzodia- 
zepin-5-one zepin-5-one 
235. 1-[(dimethylamino)- 
1-[(dimethylamino)- 
methyl]-8-chloro-4H- 
methyl]-8-chloro-6- 
s-triazolo[4,3-a]- 
phenyl-4H-s-triazolo- 
[1,5]benzodiazepin- 
[4,3-a][1,5]benzodia- 
5-one zepin-5-one 
______________________________________ 
EXAMPLE 236 
1-Methyl-8-chloro-6-(o-chlorophenyl)-4H-s-triazolo-[4,3-a][1,5-]benzodiazep 
in-5-one 
To a stirred mixture of 12.4 g of 
1-methyl-8-chloro-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one, 5 g of 
copper powder and 1 g of cupric sulfate in 100 ml of o-chlorobromobenzene 
at 90.degree. C, was added, portionwise over a 30 minute period, 4.5 g of 
potassium acetate. The reaction is heated at 165.degree. C for 9 hours and 
then worked up as described in Example 29, Method C, to give the title 
compound. 
EXAMPLES 237 - 243 
Following the procedure of Example 236 but substituting the compounds 
indicated in Column I below for 
1-methyl-8-chloro-4H-s-triazolo[4,3-a][1,5]benzodiazepin5-one in Example 
236, the compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
237. 1-methyl-4H-s-triazolo- 
1-methyl-6-(o-chloro- 
[4,3-a][1,5]benzodia- 
phenyl)-4H-s-triazolo- 
zepin-5-one [4,3-a][1,5]benzodia- 
zepin-5-one 
238. 1-methyl-8-chloro-4H- 
1-methyl-8-chloro-6- 
s-triazolo[4,3-a][1,5]- 
(o-chlorophenyl)-4H- 
benzodiazepin-5-one 
s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
239. 1-methyl-8-methoxy-4H- 
1-methyl-8-methoxy-6- 
s-triazolo[4,3-a][1,5]- 
(o-chlorophenyl)-4H-s- 
benzodiazepin-5-one 
triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
240. 1-methyl-8-(trifluoro- 
1-methyl-8-(trifluoro- 
methyl)-4H-s-triazolo- 
methyl)-6-(o-chloro- 
[4,3-a][1,5]benzodia- 
phenyl)-4H-s-triazolo- 
zepin-5-one [4,3-a][1,5]benzodia- 
zepin-5-one 
241. 1-methyl-8-nitro-4H- 
1-methyl-8-nitro-6- 
s-triazolo[4,3-a]- 
(o-chlorophenyl)-4H- 
[1,5]benzodiazepin- 
s-triazolo[4,3-a]- 
5-one [1,5]benzodiazepin-5- 
one 
242. 1-methyl-9-chloro-4H- 
1-methyl-9-chloro-6- 
s-triazolo[4,3-a]- 
(o-chlorophenyl)-4H-s- 
[1,5]benzodiazepin- 
triazolo[4,3-a][1,5]- 
5-one benzodiazepin-5-one 
243. 1-methyl-9-(trifluoro- 
1-methyl-9-(trifluoro- 
methyl)-4H-s-triazolo- 
methyl)-6-(o-chloro- 
[4,3-a][1,5]benzodia- 
phenyl)-4H-s-triazolo- 
zepin-5-one [4,3-a][1,5]benzodia- 
zepin-5-one 
244. 1,8-dimethyl-4H-s- 
1,8-dimethyl-6-(o-chloro- 
triazolo[4,3-a][1,5]- 
phenyl)-4H-s-triazolo- 
benzodiazepin-5-one 
[4,3-a][1,5]benzodiaze- 
pin-5-one 
______________________________________ 
EXAMPLE 245 
N-Benzyl-N-(2'-nitro-5'-chlorophenyl)malonamic acid, ethyl ester 
52 g of N-benzyl-N-(2-nitro-5-chlorophenyl) amine and 35.5 g of 
(chloroformyl)acetic acid ethyl ester in 500 ml benzene are refluxed for 
15 hours. The reaction is cooled, washed with dilute aqueous sodium 
bicarbonate, dried and the solvent evaporated to give the title compound. 
EXAMPLES 246 - 252 
Following the procedure of Example 245, but substituting the compounds 
indicated in Column I below for N-benzyl-N-(2-nitro-5-chlorophenyl)amine 
in Example 245, the compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
246. N-benzyl-N-[2-nitro- 
N-benzyl-N-[2'-nitro-5'- 
5-(trifluoromethyl)- 
(trifluoromethyl)phenyl]- 
phenyl amine malonamic acid ethyl 
ester 
247. N-benzyl-N-(2-nitro- 
N-benzyl-N-(2'-nitro- 
5-methylphenyl)amine 
5'-methylphenyl)malona- 
mic acid ethyl ester 
248. N-benzyl-N-(2-nitro- 
N-benzyl-N-(2'-nitro- 
5-methoxyphenyl)amine 
5'-methoxyphenyl)malona- 
mic acid ethyl ester 
249. N-benzyl-N-(2-nitro- 
N-benzyl-N-(2'-nitro- 
phenyl)amine phenyl)malonamic acid 
ethyl ester 
250. N-benzyl-N-(2-nitro- 
N-benzyl-N-(2'-nitro- 
4-chlorophenyl)amine 
4'-chlorophenyl) 
malonamic acid, ethyl 
ester 
251. N-(4-methoxybenzyl)- 
N-(4-methoxybenzyl)- 
N-(2-nitro-5-chloro- 
N-(2'-nitro-5'-chloro- 
phenyl)amine phenyl)malonamic acid 
ethyl ester 
252. N-(4-methoxybenzyl)- 
N-(4-methoxybenzyl)- 
N-[2-nitro-5-(trifluoro- 
N-[2'-nitro-5'-(tri- 
methyl)phenyl]amine 
fluoromethyl)phenyl]- 
malonamic acid, ethyl 
ester 
______________________________________ 
EXAMPLES 253 - 256 
Following the procedure of Example 245 but substituting the compounds 
indicated in column I below for (chloroformyl)acetic acid ethyl ester in 
example 245, the compounds indicated in column II are obtained. 
______________________________________ 
I II 
______________________________________ 
253. (chloroformyl)acetic 
N-benzyl-N-(2'-nitro-5'- 
acid methyl ester 
chlorophenyl)malonamic 
acid methyl ester 
254. (chloroformyl)acetic 
N-benzyl-N-(2'-nitro-5'- 
acid butyl ester chlorophenyl)malonamic 
acid butyl ester 
255. (chloroformyl)acetic 
N-benzyl-N-(2'-nitro-5'- 
acid phenyl ester 
chlorophenyl)malonamic 
acid phenyl ester 
256. (chloroformyl)acetic 
N-benzyl-N-(2'-nitro-5'- 
acid (p-methylphenyl) 
chlorophenyl)malonamic 
ester acid (p-methylphenyl)- 
ester 
______________________________________ 
EXAMPLE 257 
N-Benzyl-N-(2'-amino-5'-chlorophenyl)malonamic acid ethyl ester 
Method A 
37.6 g of N-benzyl-N-(2'-nitro-5'-chlorophenyl)malonamic acid ethyl ester 
and 0.5 g of 10% palladium-on-carbon in 200 ml ethanol containing 0.2 
moles of hydrogen chloride are hydrogenated on a Parr shaker, with 
cooling, at ambient temperature. The reaction is stopped after 0.3 moles 
of hydrogen are absorbed or when hydrogen uptake ceases, whichever comes 
first. The reaction is diluted with chloroform, filtered and the filtrate 
evaporated. The residue is suspended in methylene chloride and shaken with 
excess aqueous sodium bicarbonate. The organic phase is washed with water, 
dried and evaporated to give the title compound. 
Method B 
Following the procedure of Example 257, Method A, but substituting Raney 
nickel and methanol for the 10% palladium-on-carbon and ethanolic hydrogen 
chloride, respectively, in Example 257, Method A, and running the reaction 
at an initial hydrogen pressure of 3 atm., gives the title compound. 
EXAMPLES 258 - 268 
Following the procedure of Example 257, Methods A and B, but substituting 
the compounds indicated in Column I below for 
N-benzyl-N-(2'-nitro-5'-chlorophenyl)malonamic acid ethyl ester in Example 
257, Methods A and B, the compounds indicated in Column II are obtained. 
______________________________________ 
I II 
______________________________________ 
258. N-benzyl-N-[2'-nitro- 
N-benzyl-N-[2'-amino-5'- 
5'-(trifluoromethyl)phenyl] 
(trifluoromethyl)phenyl] 
malonamic acid ethyl ester 
malonamic acid ethyl 
ester 
259. N-benzyl-N-(2'-nitro- 
N-benzyl-N-(2'-amino- 
5'-methylphenyl) 5'-methylphenyl)malona- 
malonamic acid ethyl 
mic acid ethyl ester 
ester 
260. N-benzyl-N-(2'-nitro- 
N-benzyl-N-(2'-amino- 
5'-methoxyphenyl) 5'-methoxyphenyl) 
malonamic acid ethyl 
malonamic acid ethyl 
ester ester 
261. N-benzyl-N-(2'-nitro- 
N-benzyl-N-(2'-amino- 
phenyl)malonamic acid, 
phenyl)malonamic 
ethyl ester acid, ethyl ester 
262. N-benzyl-N-(2'-nitro- 
N-benzyl-N-(2'-amino- 
4'-chlorophenyl) 4'-chlorophenyl) 
malonamic acid, ethyl 
malonamic acid, ethyl 
ester ester 
263. N-(4'-matyoxybenzyl)- 
N(4-methoxybenzyl)- 
N-(2'-nitro-5'-chloro- 
N-(2'-amino-5'-chloro- 
phenyl)malonamic acid 
phenyl)malonamic acid 
ethyl ester ethyl ester 
264. N-(4-methoxybenzyl)-N- 
N-(4-methoxybenzyl)-N- 
[2'-nitro-5'-(trifluoro- 
[2'-amino-5'-(trifluoro- 
methyl)phenyl]malonamic 
methyl)phenyl]malonamic 
acid, ethyl ester acid, ethyl ester 
265. N-benzyl-N-(2'-nitro- 
N-benzyl-N-(2'-amino- 
5'-chlorophenyl)malona- 
5'-chlorophenyl)malonamic 
mic acid methyl ester 
acid methyl ester 
266. N-benzyl-N-(2'-nitro- 
N-benzyl-N-(2'-amino- 
5'-chlorophenyl)malona- 
5'-chlorophenyl)malona- 
mic acid butyl ester 
mic acid butyl ester 
267. N-benzyl-N-(2'-nitro- 
N-benzyl-N-(2'-amino- 
5'-chlorophenyl)malona- 
5'-chlorophenyl)malonamic 
mic acid phenyl ester 
acid phenyl ester 
268. N-benzyl-N-(2'-nitro- 
N-benzyl-N-(2'amino- 
5'-chlorophenyl)malona- 
5'-chlorophenyl)malona- 
mic acid (p-methyl- 
mic acid (p-methylphenyl) 
phenyl)ester ester 
______________________________________ 
EXAMPLES 269 - 279 
Following the procedure of Example 140, Methods B and D, but substituting 
the compounds indicated in Column I below for 
N-benzyl-N-(2'-amino-5'-chlorophenyl)malonamic acid, ethyl ester in 
Example 140, Methods B and D, the compounds indicated in Column II are 
obtained. 
______________________________________ 
269. N-benzyl-N-[2'-amino- 
7-(trifluoromethyl)-5- 
5'-(trifluoromethyl)- 
benzyl-1H-1,5-benzodia- 
phenyl]malonamic zepine-2,4-dione 
acid ethyl ester 
270. N-benzyl-N-(2'-amino- 
7-methyl-5-benzyl-1H- 
5'-methylphenyl) 1,5-benzodiazepine- 
malonamic acid 2,4-dione 
ethyl ester 
271. N-benzyl-N-(2'-amino- 
7-methoxy-5-benzyl-1H- 
5'-methoxyphenyl) 1,5-benzodiazepine- 
malonamic acid 2,4-dione 
ethyl ester 
272. N-benzyl-N-(2'-amino- 
5-benzyl-1H-1,5-benzodia- 
phenyl)malonamic zepine-2,4-dione 
acid ethyl ester 
273. N-benzyl-N-(2'-amino- 
8-chloro-5-benzyl-1H- 
4'-chlorophenyl)malona- 
1,5-benzodiazepine-2,4- 
mic acid, ethyl ester 
dione 
274. N-(4-methoxybenzyl)- 
7-chloro-5-(p-methoxy- 
N-(2'-amino-5'-chloro- 
benzyl-1H-1,5-benzodia- 
phenyl)malonamic acid 
zepine-2,4-dione 
ethyl ester 
275. N-(4-methoxybenzyl)-N- 
7-(trifluoromethyl)-5- 
[2'-amino-5'-(trifluoro- 
(p-methoxybenzyl)-1H- 
methyl)phenyl]malonamic 
1,5-benzodiazepine-2,4- 
acid, ethyl ester dione 
276. N-benzyl-N-(2'-amino- 
7-chloro-5-benzyl-1H- 
5'-chlorophenyl)malona- 
1,5-benzodiazepine-2,4- 
mic acid methyl ester 
dione 
277. N-benzyl-N-(2'-amino- 
7-chloro-5-benzyl-1H- 
5'-chlorophenyl)malona- 
1,5-benzodiazepine-2,4- 
mic acid butyl ester 
dione 
278. N-benzyl-N-(2'-amino- 
7-chloro-5-benzyl-1H- 
5'-chlorophenyl)malona- 
1,5-benzodiazepine-2,4- 
mic acid phenyl ester 
dione 
279. N-benzyl-N-(2'-amino- 
7-chloro-5-benzyl-1H- 
5'-chlorophenyl)malona- 
1,5-benzodiazepine-2,4- 
mic acid (p-methyl- 
dione 
phenyl)ester 
______________________________________ 
EXAMPLE 280 
2,7-Dichloro-5-phenyl-3H-1,5-benzodiazepin-4-one 
Method A 
28.6 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione and 20.8 g of 
phosphorus pentachloride in 1000 ml of benzene is stirred for 10 hours, 
then refluxed for 3 hours. The reaction is evaporated, azeotroped with 
benzene and the solvent evaporated. The residue is stirred with carbon 
tetrachloride and the title compound filtered off and dried. 
Method B 
To 28.6 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione and 24.2 g 
of dimethylaniline in 200 ml of benzene is added 10.2 g of phosphorous 
oxychloride. The reaction mixture is refluxed for 14 hours under argon, 
cooled to 7.degree. C, diluted with 100 ml of cold water and stirred for 
0.25 hour. The organic layer is separated, washed with 100 ml of cold 
water, dried and evaporated. The residue is stirred with 50 ml of carbon 
tetrachloride and the title compound is filtered off and dried. 
EXAMPLE 281 
Acetic acid 2-(7-chloro-5-phenyl-3H-1,5-benzodiazepin4-one-2-yl)hydrazide 
Method A 
3.0 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepin4-one-2-thione and 1.8 g of 
acetic acid hydrazide in 100 ml ethanol is refluxed for 24 hours. During 
this time a slow stream of nitrogen is bubbled through the reaction 
mixture. The mixture is evaporated, the residue taken up in methylene 
chloride, washed with water, dried and the solvent evaporated. The residue 
is chromatographed on 10-1000.mu. silica gel plates (20 .times. 20 cm) 
with acetone-methanol (9:1) eluant. The band containing the product is 
removed and stirred with acetone-methanol (4:1). The silica gel is 
filtered off and the filtrate evaporated to give the title compound. 
Method B 
3.0 g of 2-hydrazino-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one and 1.4 g 
of ethyl 1-acetoxyformate in 50 ml tetrahydrofuran containing one drop of 
N-methylmorpholine is stirred at room temperature for 24 hours. The 
reaction mixture is evaporated to give the title compound. Further 
purification is accomplished, if necessary, by chromatography as described 
in Example 281, Method A. 
EXAMPLE 282 
2-Hydrazino-7-chloro-5-3H-1,5-benzodiazepin-4-one 
Method A 
3.8 g of 
2-[2(t-butoxycarbonyl)hydroazino]-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4 
-one and 1.78 g of hydrogen bromide in 200 ml methylene chloride is stirred 
for 2 hours. The reaction mixture is washed with aqueous sodium 
bicarbonate, water, dried and evaporated. The product is stirred with 
carbon tetrachloride and the title compound is filtered off and dried. 
Method B 
4.32 g of 
2-[2-(benzyloxycarbonyl)hydrazino]-7-chloro-5-phenyl-3H-1,5-benzodiazepin- 
4-one in 400 ml 1,2-dimethoxy-ethane containing 0.4 g of 10% 
palladium-on-carbon is hydrogenated at 40 p.s.i. hydrogen pressure until 
0.01 moles of hydrogen are absorbed. The reaction is filtered, the 
filtrate evaporated at room temperature and the residue stirred with 
carbon tetrachloride to give the title compound. 
EXAMPLE 283 
2-[2-(t-butoxycarbonyl)hydrazino]-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4- 
one 
3.16 g of 2-(methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one and 
1.41 g of t-butylcarbazate in 60 ml of dimethyl formamide are refluxed for 
20 hours while a slow stream of nitrogen is bubbled through the reaction. 
The reaction is worked up as described in Example 29, Method A, to give 
the title compound. 
EXAMPLE 284 
2-[2-(Benzyloxycarbonyl)hydrazino]-7-chloro-5-phenyl-3-H-1,5-benzodiazepin- 
4-one 
Following the procedure of Example 283, but substituting benzylcarbazate 
for t-butylcarbazate in Example 283, the title compound is obtained. 
EXAMPLE 285 
7-Amino-5-phenyl-1H-1,5-benzodiazepine-2,4-dione 
29.7 g of 7-nitro-5-phenyl-1-H-1,5-benzodiazepine-2,4-dione in 200 ml 
ethanol containing 1.0 g of Raney nickel is hydrogenated at room 
temperature at an initial hydrogen pressure of 50 p.s.i. The reaction is 
stopped after 0.3 moles of hydrogen has been absorbed. The reaction 
mixture is filtered and the filtrate evaporated to give 
7-amino-5-phenyl-3H-1,5-benzodiazepine-2,4-dione. 
EXAMPLE 286 
7-Diazonium-5-phenyl-1H-1,5-benzodiazepin-4-one, sulfate 
20 g of 7-amino-5-phenyl-1H-1,5-benzodiazepine-2,4-dione in 100 ml of 
acetic acid is added to a solution of 7.62 g of nitrosysulfuric acid in 10 
ml of acetic at 0.degree. C. After 30 minutes, 100 ml of ether is added, 
with stirring and cooling, and the precipitated diazonium sulfate is 
filtered off and dried. 
EXAMPLE 287 
7-(Methylthio)-5-phenyl-1H-1,5-benzodiazepine-2,4-dione 
3.76 g of 7-diazonium-5-phenyl-1H-1,5-benzodiazepine-2,4-dione sulfate is 
added portionwise with stirring under a dry-ice condenser, to a solution 
of 2.58 g of potassium methyl mercaptide in 100 ml of methyl mercaptan. 
The reaction is gently refluxed for 24 hours. The reaction is evaporated; 
the residue diluted with 200 ml of methylene chloride, washed with a 
solution of 1.35 g acetic acid in 100 ml water, dried and evaporated to 
give the title compound. The product may be further purified by 
chromatography on silica gel (e.g. 200-1000.mu., 20 .times. 20 cm plates) 
using chloroform-ethyl acetate (6:4) as eluting solvent. The band 
containing the title compound is removed, stirred with EtOAc-MeOH (9:1) 
and the silica gel is filtered off. The filtrate is evaporated to give the 
title compound. 
EXAMPLE 288 
1-Methyl-8-(methylsulfinyl)-6-phenyl-4H-s-triazolo-[4,3-a][1,5]benzodiazepi 
n-5-one 
3.36 g of 
1-methyl-8-(methylthio)-6-phenyl-4-H-s-triazolo[4,3-a][1,5]benzodiazepin-5 
-one and 2.14 g of sodium metaperiodate in 500 ml methanol is stirred at 
+5.degree. C for 24 hours. The reaction is evaporated; the residue 
dissolved in methylene chloride, washed with water, dried and 
concentrated. The concentrate is chromatographed on silica gel 
(20-1000.mu. plates, 20 .times. 20 cm) using acetone-methanol (9:1) as 
eluting solvent. The band containing the product is removed, stirred with 
acetone-methanol (4:1) and the silica gel filtered off. The filtrate is 
evaporated to give the title compound. 
EXAMPLE 289 
1-Methyl-8-amino-6-phenyl-4H-s-triazolo[4,3-a][1,5]-benzodiazepin-5-one 
33.5 g of 1-methyl-8-nitro-6-phenyl-4H-s-triazolo[4,3-a][1,5] 
benzodiazepin-5-one in 100 ml of ethanol containing 2.0 g of Raney nickel 
is hydrogenated at room temperature at an initial hydrogen pressure of 50 
p.s.i. The reaction is stopped when 0.3 moles of hydrogen has been 
absorbed; the suspension is filtered and the filtrate evaporated to give 
the title compound. 
EXAMPLE 290 
1-Methyl-8-acetamido-6-phenyl-4-H-s-triazolo[4,3-a][1,5]-benzodiazepin-5-on 
3.47 g of 
1-methyl-8-amino-6-phenyl-4-H-s-triazolo-[4,3-a][1,5]benzodiazepin-5-one 
and 1.02 g of acetic anhydride in 50 ml pyridine is stirred for 12 hours 
then refluxed for 30 minutes. The reaction is evaporated; the residue is 
taken up in chloroform, washed with dilute aqueous sodium bicarbonate, 
with water and dried. The solvent is evaporated to give the title 
compound. 
EXAMPLE 291 
4-Hydroxyl-1-methyl-8-chloro-6-phenyl-4H-s-triazolo-[4,3-a][1,5]benzodiazep 
in-5-one 
44.6 g of 
4-(benzyloxy)-1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodia 
zepin-5-one in 400 ml of ethanol containing 2.0 g of Raney nickel is 
hydrogenated at an initial hydrogen pressure of 40 p.s.i. After 0.1 mole 
of hydrogen has been absorbed, the reaction is stopped, filtered and the 
solvent evaporated. The residue is triturated in ether and the title 
compound filtered off and dried. 
EXAMPLES 292 - 296 
Following the procedure of Example 124, but substituting the compounds 
indicated in column I below for diethylamine in example 124, the compounds 
in column II are obtained. 
______________________________________ 
I II 
______________________________________ 
292. 4-phenylpiperdine 
1-(4-phenylpiperdinomethyl)- 
8-chloro-6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodiazepin-5-one 
293. N-methylpiperazine 
1-(4-methylpiperazinomethyl)- 
8-chloro-6-phenyl-4H-s-trazolo 
[4,3-a][1,5]benzodiazepin-5-one 
294. N-(methoxyphenyl)- 
1-[4-(2-methoxyphenyl)piperazino- 
piperazine methyl]-8-chloro-6-phenyl-4H- 
s-trazolo[4,3-a][1,5]benzodiazepin- 
5-one 
295. silver nitrite 1-(nitromethyl)-8-chloro-6-phenyl- 
4H-s-triazolo[4,3-a][1,5]benzo- 
diazepin-5-one 
296. N-(t-butoxycarbonyl)- 
1-[4-(t-butoxycarbonyl)- 
piperazine piperazinomethyl]-8-chloro-6- 
phenyl-4H-s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
______________________________________ 
EXAMPLE 297 
1-Piperazinomethyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]-benzodiazepi 
n-5-one 
2 g. of 
1-[4-(t-butoxycarbonyl)-piperazinomethyl]-8-chloro-6-phenyl-4-H-s-triazolo 
[4,3-a][1,5]benzodiazepin-5-one in 50 ml of trifluoroacetic acid is stirred 
for 2 hours. The reaction mixture is evaporated and the residue 
partitioned between methylene chloride and aqueous sodium bicarbonate. The 
organic phase is washed with water, dried and evaporated to give the title 
compound. 
EXAMPLE 298 
4-(3,4,5-trimethoxybenzoyloxy)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]b 
enzodiazepin-5-one 
Following the procedure of example 281, method B, but substituting ethyl 
1-(3,4,5-trimethoxybenzoyloxy)formate for ethyl 1-acetoxyformate and 
4-hydroxy-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one 
for 2-hydrazino-7chloro-5 -phenyl-3H-1,5-benzodiazepin-4-one in example 
281, method B, the title compound is obtained. 
EXAMPLE 299 
1-Methyl-8-chloro-6-(2',4'-dichlorophenyl)-4H-s-triazolo-[4,3-a][1,5]benzod 
iazepin-5-one 
Part A 
20 g of 2',4',5-trichloro-2-nitrodiphenylamine in 100 ml of methanol 
containing 0.2 g of Raney nickel is hydrogenated at an initial hydrogen 
pressure of 7 atm. until three molar equivalents of hydrogen is consumed. 
The suspension is filtered and the filtrate evaporated to give 
2',4',5-trichloro-2-aminodiphenylamine. 
Part B 
Following the procedure of example 140, method A, but substituting the 
above produced 2',4',5-trichloro-2-aminodiphenylamine for 
2-benzylamino-4-chloro-aniline in example 140, method A, gives 
7-chloro-(2',4'-dichlorophenyl)-1H-1,5-benzodiazepin-2,4-dione. 
Part C 
Following the procedure of example 1 but substituting the above produced 
7-chloro-5-(2',4'-dichlorophenyl)-1H-1,5-benzodiazepin-2,4-dione for 
7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione in example 1, gives 
7-chloro-5-(2',4'-dichlorophenyl)-1H-1,5-benzodiazepin-4-one-2-thione. 
Part D 
Following the procedure of example 29, method A, but substituting the above 
produced 
7-chloro-5-(2',4'-dichlorophenyl)-1H-1,5-benzodiazepin-4-one-2-thione for 
7-chloro-5phenyl -1-H-1,5-benzodiazepin-4-one-2-thione in example 29, 
method A, gives the title compound of formula 1. 
EXAMPLES 300 - 318 
Following the procedure of parts A to D of the foregoing example but 
employing as starting materials the substituted compound of formula 15 
where m is zero wherein the substituents and the position they occupy are 
indicated below: 
__________________________________________________________________________ 
Example 
No. 3 4 5 6 2' 3' 
4' 5' 6' 
__________________________________________________________________________ 
300. Cl Cl 
301. Cl 
302. Cl CH.sub.3 SO.sub.2 
303. CF.sub.3 Cl CF.sub.3 
304. Cl CH.sub.3 
CH.sub.3 
305. Cl CH.sub.3 
Cl 
306. CH.sub.2 S Cl 
307. Cl Cl CH.sub.3 
308. Cl Cl 
309. CH.sub.3 O 
CH.sub.3 O 
310. Cl Cl Cl 
311. Cl OCH.sub.3 OCH.sub.3 
312. Cl 
313. Cl Cl 
314. CH.sub.3 O CH.sub.3 O 
315. Cl CH.sub.3 
316. CH.sub.3 SO.sub.2 
317. Cl CH.sub.3 S 
318. Cl CH.sub.3 SO.sub.2 
319. Cl F F 
__________________________________________________________________________ 
there is obtained the correspondingly substituted compound of formula I 
wherein the substitutents and the position they occupy are indicated 
below: 
__________________________________________________________________________ 
Example 
No. 7 8 9 10 2' 3' 4' 5' 6' 
__________________________________________________________________________ 
300. Cl Cl 
301. Cl 
302. Cl CH.sub.3 SO.sub.2 
303. CF.sub.3 Cl CF.sub.3 
304. Cl CH.sub.3 
CH.sub.3 
305. Cl CH.sub.3 
Cl 
306. CH.sub.3 S Cl 
307. Cl Cl CH.sub.3 
308. Cl Cl 
309. CH.sub.3 O 
CH.sub.3 O 
310. Cl Cl Cl 
311. Cl OCH.sub.3 OCH.sub.3 
312. Cl 
313. Cl Cl 
314. OCH.sub.3 OCH.sub.3 
315. CH.sub.3 
Cl 
316. CH.sub.3 SO.sub.2 
317. Cl SCH.sub.3 
318. Cl CH.sub.3 SO.sub.2 
319. CL F F 
__________________________________________________________________________ 
EXAMPLE 320 
1-Methyl-8-(methylsulfonyl)-6-phenyl-4H-s-triazolo-[4,3-a][1,5]benzodiazepi 
n-5-one 
Following the procedure of example 288, but using 4.14 g instead of 2.14 g 
of sodium metaperiodate, the title compound is obtained. 
EXAMPLE 321 
4-Chloro-2',6'-difluoro-2-nitrophenylamine 
19.1 g of 2,4-dichloronitrobenzene and 126.0 g of 2,6-difluoroaniline and 
16.4 g of sodium acetate are refluxed for 24 hours. After cooling, the 
reaction is poured into excess dilute hydrochloric acid, extracted with 
ether and the ether is then dried and evaporated. The residue from the 
ether phase is chromatographed on neutral alumina with hexane-ether (9:1). 
The eluant is evaporated. The title compound is purified by 
recrystallization from ethanol. 
EXAMPLE 322 
1-Methyl-8-chloro-6-(5'-chloro-2'-nitrophenyl)-4H-s-triazolo[4,3-a][1,5]ben 
zodiazepin-5-one 
Following the procedure of parts B through D of example 299, but 
substituting 2-amino-5'-chloro-2'-nitrodiphenylamine for 
2',4',5-trichloro-2-aminodiphenyl-amine in part B, the title compound is 
obtained. 
EXAMPLE 323 
1-Ethoxymethyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,4]-benzodiazepin-5- 
one 
Following the procedure of example 124, but substituting sodium ethoxide 
and ethanol for diethylamine in example 124, the title compound is 
obtained. 
EXAMPLE 324 
4-(2-Dimethylaminoethyl)-1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a] 
[1,5]benzodiazepin-5-one 
37.0 g of 
1-methyl-8-chloro-6-phenyl-4H-s-triazolo-[4,3-a][1,5]benzodiazepin-5-one 
and 7.8 g of a 50 percent sodium hydride mineral oil dispersion in 400 ml 
of dry 1,2-dimethoxyethane are stirred for 2 hours. A solution of 13.7 g 
of 2-dimethylaminoethyl bromide in 40 ml of dry 1,2-dimethoxyethane is 
added and the whole is stirred for 18 hours. The solvent is evaporated and 
the residue is partitioned between methylene chloride and water. The 
organic phase is washed with water, dried and evaporated to give the title 
compound. 
EXAMPLES 325-338 
Following the procedure of example 324 but substituting the compounds 
indicated in column I below for 2-dimethylaminoethyl bromide in example 
324, the compounds indicated in column II are obtained: 
__________________________________________________________________________ 
I II 
__________________________________________________________________________ 
325. 
3-dimethylaminopropyl 
4-(3-dimethylaminopropyl)-1- 
chloride methyl-8-chloro-6-phenyl-4H-s- 
triazolo[4,3,-a][1,5]benzodia- 
zepin-5-one 
326. 
2-pyrrolidinoethyl 
4-(2-pyrrolidinoethyl)-1- 
chloride methyl-8-chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]benzodia- 
zepin-5-one 
327. 
2-diethylaminoethyl 
4-(2-diethylaminoethyl)-1- 
bromide methyl-8-chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]benzodia- 
zepin-5-one 
328. 
2-morpholinoethyl 
4-(2-morpholinoethyl)-1-methyl- 
chloride 8-chloro-6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodiazepin-5- 
one 
329. 
2-piperidinoethyl 
4-(2-piperidinoethyl)-1- 
chloride methyl-8-chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]benzodia- 
zepin-5-one 
330. 
2-(4-phenylpiperi- 
4-[2-(4-phenylpiperidino)ethyl]- 
dino)ethyl chloride 
1-methyl-8-chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]benzodia- 
zepin-5-one 
331. 
2-piperazinoethyl 
4-(2-piperazinoethyl)-1-methyl- 
chloride 8-chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]benzodia- 
zepin-5-one 
332. 
2-(4-methylpiperazino)- 
4-[2-(4-methylpiperazino)ethyl] 
ethyl chloride 1-methyl-8-chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]benzodia- 
zepin-5-one 
333. 
2-(4-phenylpiperazino)- 
4-[2-(4-phenylpiperazino)ethyl] 
ethyl chloride 1-methyl-8-chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]benzodiazepin- 
5-one 
334. 
3-[4-(2-methoxyphenyl)- 
4-[3-[2-methoxyphenyl)pipera- 
piperazino]propyl- 
zino]propyl]-1-methyl-8-chloro- 
chloride 6-phenyl-4H-s-triazolo[4,3-a]- 
[1,5]benzodiazepin-5-one 
335. 
3-piperidinopropyl 
4-(3-piperidinopropyl)-1-methyl- 
chloride 8-chloro-6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodiazepin-5-one 
336. 
3-methylpipera- 
4-[3-(4-methylpiperazino)propyl]- 
zino)propyl chloride 
1-methyl-8-chloro-6-phenyl-4H- 
s-triazolo[4,3-a][1,5]benzodia- 
zepin-5-one 
337. 
2-(N-benzyl-N- 4-[2-(N-benzyl-N-methylamino)ethyl]- 
methylamino)ethyl 
1-methyl-8-chloro-6-phenyl-4H- 
chloride s-triazolo[4,3-a][1,5]benzodia- 
zepin-5-one 
338. 
3-[(t-butoxycarbonyl)- 
4-[3-[(t-butoxycarbonyl)amino]- 
amino]propyl chloride 
propyl]-1-methyl-8-chloro-6- 
phenyl-4H-s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
__________________________________________________________________________ 
EXAMPLE 339 
4-(2-Methylaminoethyl)-1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5] 
benzodiazepin-5-one 
4 g of 
4-[2-(N-benzyl-N-methylamino)ethyl]-1-methyl-8-chloro-6-phenyl-4H-s-triazo 
lo[4,3-a][1,5]benzodiazepin-5-one in 100 ml of ethanol containing 0.4 g of 
Raney nickel is hydrogenated at 50 p.s.i. hydrogen pressure until 0.0085 
moles of hydrogen is absorbed. The suspension is filtered and the filtrate 
is evaporated. The residue is triturated with a small amount of cold ether 
and the title compound is filtered off and dried. 
EXAMPLE 340 
4-(3-aminopropyl)-1-methyl-8-chloro-6-phenyl-4H-s-triazolo-[4,3-a][1,5]benz 
odiazepin-5-one 
2.5 g of 
4-[2-(N-t-butoxycarbonylamino)propyl]-1-methyl-8-chloro-6-phenyl-4H-s-tria 
zolo[4,3-a][1,5]benzodiazepin-5-one in 50 ml of trifluoroacetic acid is 
stirred at room temperature for 2 hours. The reaction is evaporated and 
the residue is stirred with a solution of 1.9 g of sodium bicarbonate in 
400 ml of methanol-water (10:1). After 3 hours the reaction is evaporated 
and the residue is partitioned between methylene chloride and water. The 
methylene chloride is washed with water, dried and evaporated to give the 
title compound. 
EXAMPLES 341-343 
Following the procedure of example 29, Method A, but substituting the 
compounds indicated in column I below for acetic acid hydrazide in example 
29, Method A, the compounds indicated in column II are obtained. 
__________________________________________________________________________ 
I II 
__________________________________________________________________________ 
341. 
picolinic acid hydrazide 
1-(2-pyridyl)-8-chloro-6-phenyl- 
4H-s-triazolo[4,3-a][1,5]benzo- 
diazepin-5-one 
342. 
nicotinic acid hydrazide 
1-(3-pyridyl)-8-chloro-6-phenyl- 
4H-s-triazolo[4,3-a][1,5]benzo- 
diazepin-5-one 
343. 
isonicotinic acid 
1-(4-pyridyl)-8-chloro-6-phenyl- 
hydrazide 4H-s-triazolo[4,3-a][1,5]benzo- 
diazepin-5-one 
343. 
m-(trifluoromethyl)benzoic 
1-[3-(trifluoromethyl)phenyl]-8- 
acid hydrazide 
chloro-6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodiazepin-5-one 
344. 
o-chlorobenzoic acid 
1-(2-chlorophenyl)-8-chloro- 
hydrazide 6-phenyl-4H-s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
345. 
p-methylbenzoic acid 
1-(4-methylphenyl)-8-chloro-6- 
hydrazide phenyl-4H-s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
346. 
m-methoxybenzoic acid 
1-(3-methoxyphenyl)-8-chloro-6- 
hydrazide phenyl-4H-s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
347. 
m-nitrobenzoic acid 
1-(3-nitrophenyl)-8-chloro-6- 
hydrazide phenyl-4H-s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
348. 
p-acetamidobenzoic 
1-(4-acetamidophenyl)-8-chloro-6- 
acid hydrazide 
phenyl-4H-s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
349. 
o-(methylthio)benzoic 
1-[2-(methylthio)phenyl]-8-chloro- 
6-phenyl-4H-s-triazolo[4,3-a][1,5]- 
benzodiazepin-5-one 
350. 
p-(methylsulfonyl)- 
1-[4-(methylsulfonyl)phenyl]-8- 
benzoic acid hydrazide 
chloro-6-phenyl-4H-s-triazolo- 
[4,3-a][1,5]benzodiazepin-5-one 
__________________________________________________________________________ 
EXAMPLE 351 
A group of experimental animals composed of rats, mice and monkeys are 
orally administered 
1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one. 
The compound is administered at the following dosage levels: rats, 3.1 
mg/kg; mice, 1 mg/kg; monkeys, 2.5 mg/kg. Ataxia is produced in all of the 
animals of the test group at the dosage levels indicated. 
EXAMPLE 352 
A group of rats is orally administered 
1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one. 
The group is then subjected to the conflict test procedure described by 
Vogel et al., Psychopharmacologist, 21, 1 (1970). A tranquilizing effect 
is produced in all of the test animals. 
EXAMPLE 353 
A group of mice is orally administered 
1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one at 
a dosage level of 12 mg/kg. At this dosage level the convulsant effect of 
135 mg of subcutaneously administered pentylenetetrazole is antagonized in 
50% of the animals. 
EXAMPLE 354 
In another test, the same group of mice is orally administered 26 mg/kg of 
the foregoing compound. This dosage level antagonizes the convulsant 
effect of 75 mg of intravenously administered strychnine in 50% of the 
test animals. 
EXAMPLE 355 
A group of mice are orally administered 30 mg/kg of 
1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one. 
Food consumption is increased in the test animals by 100% compared to a 
group of control animals. 
EXAMPLE 356 
Preparation of capsule formulation 
______________________________________ 
Ingredient Milligrams per Capsule 
______________________________________ 
1-Methyl-8-chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]benzodiazepin-5-one 
400 
Starch 80 
Magnesium stearate 5 
______________________________________ 
The active ingredient, starch and magnesium stearate are blended together. 
The mixture is used to fill hard shell capsules of a suitable size at a 
fill weight of 485 milligrams per capsule. 
EXAMPLE 357 
Preparation of tablet formulation 
______________________________________ 
Ingredient Milligrams per Tablet 
______________________________________ 
1-Methyl-8-chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]benzodiazepin-5-one 
300 
Lactose 200 
Corn starch (for mix) 
50 
Corn starch (for paste) 
50 
Magnesium stearate 6 
______________________________________ 
The active ingredient, lactose and corn starch (for mix) are blended 
together. The corn starch (for paste) is suspended in water at a ratio of 
10 grams of corn starch per 80 milliliters of water and heated with 
stirring to form a paste. This paste is then used to granulate the mixed 
powders. The wet granules are passed through a No. 8 screen and dried at 
120.degree. F. The dry granules are passed through a No. 16 screen. The 
mixture is lubricated with magnesium stearate and compressed into tablets 
in a suitable tableting machine. Each tablet contains 300 milligrams of 
active ingredient. 
EXAMPLE 358 
Preparation of oral syrup formulation 
______________________________________ 
Ingredient Amount 
______________________________________ 
1-Methyl-8-chloro-6-phenyl-4H-s- 
triazolo[4,3-a][1,5]benzodiazepin-5-one 
500 mg. 
Sorbitol solution (70% N.F.) 
40 ml. 
Sodium benzoate 150 mg. 
Sucaryl 90 mg. 
Saccharin 10 mg. 
Red Dye (F.D. & Co. No. 2) 
10 mg. 
Cherry flavor 50 mg. 
Distilled water qs to 100 ml. 
______________________________________ 
The sorbitol solution is added to 40 milliliters of distilled water and the 
active ingredient is suspended therein. The sucaryl, saccharin, sodium 
benzoate, flavor and dye are added and dissolved in the above solution. 
The volume is adjusted to 100 milliliters with distilled water. 
Other ingredients may replace those listed in the above formulation. For 
example, a suspending agent such as bentonite magma, tragacanth, 
carboxymethylcellulose, or methylcellulose may be used. Phosphates, 
citrates or tartrates may be added as buffers. Preservatives may include 
the parabens, sorbic acid and the like and other flavors and dyes may be 
used in place of those listed above.