4H-pyrazolo[1 ,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H)one and derivatives thereof

New 4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido-[3,4-e]pyrimidin-5(8H)one and new derivatives thereof have the general formula ##STR1## The compounds are useful as anti-inflammatory agents and central nervous system depressants.

SUMMARY OF THE INVENTION 
This invention relates to the new compounds 
4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one, new 
derivatives and salts thereof. These new compounds have the general 
formula 
##STR2## 
R.sup.1 is hydrogen, lower alkyl, phenyl, phenyl-lower alkylene, benzoyl 
or substituted benzoyl. 
R.sup.2 is hydrogen or lower alkyl. 
R.sup.3 is hydrogen, lower alkyl or phenyl. 
R.sup.4 is hydrogen or lower alkyl. 
R.sup.5 is hydrogen, lower alkyl, phenyl-lower alkylene, benzoyl or 
substituted benzoyl, lower alkanoyl, lower alkoxy-lower alkylene, lower 
alkylthio-lower alkylene, phenyl or substituted phenyl, amino-lower 
alkylene or di-lower alkylamino-lower alkylene. The basic amino group may 
also form one of the heterocycles piperidine, morpholine, thiamorpholine 
or piperazine. 
R.sup.6 is hydrogen or lower alkyl. 
DETAILED DESCRIPTION OF THE INVENTION 
The various groups represented by the symbols are of the following types: 
The lower alkyl groups are straight or branched chain hydrocarbon groups 
having up to seven carbon atoms like methyl, ethyl, propyl, isopropyl, 
butyl, isobutyl, t-butyl, pentyl and the like. The lower alkylene groups 
are divalent radicals of the same kind. Examples of the phenyl-lower 
alkylene groups are benzyl, phenethyl, phenylisopropyl and the like. The 
C.sub.1 -C.sub.4 and especially the C.sub.1 -C.sub.2 lower alkyl and lower 
alkylene groups are preferred. 
The substituted Phenyl and substituted benzoyl groups (i.e., R.sub.9 
-phenyl, R.sub.9 -benzoyl) are simply substituted benzoyl groups having 
halogen (the four common halogens, but preferably chlorine or bromine), 
lower alkyl or lower alkoxy (similar to the lower alkyl groups defined 
above) groups (R.sub.9) on the phenyl ring, for example, p-chlorophenyl, 
o-chlorophenyl, p-bromophenyl, m-chlorophenyl, m-bromophenyl, p-tolyl, 
o-tolyl, o-ethylphenyl, p-methoxyphenyl, p-chlorobenzyl, o-chlorobenzoyl, 
p-bromobenzoyl, m-bromobenzoyl, p-methylbenzoyl, o-ethylbenzoyl, 
p-methoxybenzoyl and the like. Chlorine, bromine and methyl are the 
preferred substituents in both instances. 
The lower alkanoyl groups are the acyl groups of the lower (C.sub.2 
-C.sub.7) fatty acids, e.g., acetyl, propionyl, butyryl, isobutyryl and 
the like. Those with up to four carbons in the chain are preferred, 
especially acetyl. 
The lower alkoxy-lower alkylene and lower alkylthiolower alkylene groups 
represented by R.sup.5 have radicals like those described above including 
such groups as methoxymethylene, ethoxymethylene, methoxyethylene, 
methylthiomethylene, methylthioethylene, ethylthiomethylene, 
ethylthioethylene, etc. 
The amino-lower alkylene groups are of the same type, e.g., aminomethyl, 
aminoethyl, etc. The di-lower alkylaminolower alkylene groups are also of 
the same type wherein the nitrogen is substituted with two lower alkyl 
groups. In addition, the two lower alkyl groups may join in forming a 
heterocycle which may include an additional hetero atom. In other words, 
the di-lower alkylamino-lower alkylene group can take the form 
##STR3## 
alkylene wherein R.sup.7 and R.sup.8 are lower alkyl groups or join 
together to complete the heterocycle piperidine, morpholine, piperazine or 
thiamorpholine (preferably the first three and especially the first two). 
Preferably the lower alkyl and lower alkylene groups have up to 4 and 
especially 1 or 2 carbons. Thus, groups like dimethylaminomethyl, 
diethylaminomethyl, dimethylaminoethyl, diethylaminoethyl, 
dimethylaminopropyl, piperidinomethyl, piperidinoethyl, morpholinomethyl, 
morpholinoethyl, thiamorpholinomethyl, thiamorpholinoethyl, 
piperazinomethyl, piperazinoethyl, piperazinopropyl are included. 
Preferably R.sup.1 is lower alkyl, especially ethyl; R.sup.2 is hydrogen or 
lower alkyl, especially hydrogen; R.sup.3 is hydrogen or lower alkyl, 
especially methyl; R.sup.4 is hydrogen or lower alkyl, especially 
hydrogen; R.sup.5 is lower alkyl, especially methyl, ethyl and isopentyl, 
or di-lower alkylaminolower alkylene, especially dimethylaminopropyl and 
dimethylaminoethyl; R.sup.6 is lower alkyl or hydrogen, especially 
hydrogen. 
The products of the examples are representative of the various compounds of 
this invention and constitute especially preferred embodiments. 
The new compounds of formula I are formed by the following series of 
reactions. The symbols in the structural formulas have the same meaning as 
previously described. 
A pyrazolo[3,4-b]pyridine of the formula 
##STR4## 
(produced according to the procedure given in U.S. Pat. No. 3,761,487, 
Sept. 25, 1973) is made to react with an iminonitrile of the formula. 
##STR5## 
or a ketonitrile of formula 
##STR6## 
in an organic solvent like alcohol, or the like. 
By this reaction a hydrazone of the formula 
##STR7## 
is produced. A compound of formula I wherein R.sup.5 is hydrogen is now 
obtained by treating the compound of formula V in an organic acid, like 
acetic acid with zinc chloride or any other Lewis acid as catalyst. 
Alternatively, the ring closure may be effected under basic conditions, 
e.g., with an alkali metal alcoholate in the corresponding alcohol like 
sodium or potassium alcoholate in ethyl alcohol. 
Compounds of formula I, wherein R.sup.5 is other than hydrogen, are 
obtained by treatment of a cyclized compound of formula I wherein R.sup.5 
is hydrogen, obtained as just described, with the halide R.sup.5 -hal, 
wherein hal is a halogen, preferably chlorine or bromine, and R.sup.5 has 
the meaning defined above, in the presence of a base, preferably a base of 
an alkali metal, like sodium hydride, sodium or potassium alcoholate, 
sodium metal, sodium or potassium hydroxide, or the like, in a solvent 
like dimethylformamide or diethyleneglycol dimethyl ether. 
The new compounds of formula I form salts which are also part of this 
invention. The salts include acid addition salts, particularly the 
non-toxic, physiologically acceptable members. These salts are formed by 
reaction with one or more equivalents of a variety of inorganic and 
organic acids providing acid addition salts including, for example, 
hydrohalides (especially hydrochloride and hydrobromide), sulfate, 
nitrate, borate, phosphate, oxalate, tartrate, maleate, citrate, acetate, 
ascorbate, succinate, aryl- and alkanesulfonates like benzenesulfonate, 
methanesulfonate, cyclohexanesulfamate and toluenesulfonate, etc. The acid 
addition salts frequently provide a convenient means for isolating the 
product, e.g., by forming and precipitating a salt (which is not 
necessarily non-toxic) in an appropriate medium in which the salt is 
insoluble, then after separation of the salt, neutralizing with a base 
such as barium hydroxide or sodium hydroxide, to obtain the free base of 
formula I. Other salts can then be formed from the free base by reaction 
with an equivalent or more of acid containing the desired anion. 
Additional experimental details are found in the examples. 
The new compounds of this invention have central nervous system depressant 
activity and can be used as psychotropic agents, e.g., as ataractic agents 
for the relief of anxiety and tension states, for example, in mice, cats, 
rats, dogs and other mammalian species. For this purpose a compound or 
mixture of compounds of formula I, or non-toxic, physiologically 
acceptable acid addition salt thereof, is preferably administered orally, 
but parenteral routes such as subcutaneously, intramuscularly, 
intravenously or intraperitoneally in the described dosages, can also be 
employed. A single dose, or preferably 2 to 4 divided daily doses, 
provided on a basis of about 1 to 50 mg. per kilogram per day, preferably 
about 2 to 15 mg. per kilogram per day, is appropriate. 
The new compounds of this invention also have antiinflammatory properties 
and are useful as anti-inflammatory agents, for example, to reduce local 
inflammatory conditions such as those of an edematous nature or resulting 
from proliferation of connective tissue in various mammalian species such 
as rats, dogs and the like when given orally in dosages of about 5 to 50 
mg/kg/day, preferably 5 to 25 mg/kg/day, in single or 2 to 4 divided 
doses, as indicated by the carageenan edema or delayed hypersensitivity 
skin reaction tests in rats. 
The compounds of the invention can be utilized by formulation in 
compositions such as tablets, capsules or elixirs for oral administration 
or in sterile solutions or suspensions for parental administration. About 
10 to 250 mg. of a compound or mixture of compounds of formula I or 
physiologically acceptable acid addition salt is compounded with a 
physiologically acceptable vehicle, carrier, excipient, binder, 
preservative, stabilizer, flavor, etc., in a unit dosage form as called 
for by accepted pharmaceutical practice. The amount of active substance in 
these compositions or preparations is such that a suitable dosage in the 
range indicated is obtained. 
Illustrative of the adjuvants which may be incorporated in tablets, 
capsules and the like are 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; a sweetening agent 
such as sucrose, lactose or saccharin; a flavoring agent such as 
peppermint, oil of wintergreen or cherry. 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 or capsules may be coated with shellac, sugar or 
both. A syrup or elixir may contain the active compound, 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 the dosage unit should be pharmaceutically pure and 
substantially non-toxic in the amounts employed. 
For topical administration as an anti-inflammatory agent, a conventional 
lotion, ointment or cream containing about 0.1 to 3 percent by weight of a 
compound of formula I or its salt is formulated.

The following examples are illustrative of the invention and constitute 
especially preferred embodiments. They also serve as models for the 
preparation of other members of the group which can be produced by 
suitable substitution of starting materials. All temperatures are in 
degrees celsius. 
EXAMPLE 1 
2,4-Dimethyl-8-ethyl-4H-pyrazolo[1,5-a]pyrazolo[4', 
3':5,6]-pyrido[3,4-e]pyrimidin-5(8H)-one 
a. 
4-[2-(2-cyano-1-methylethylidene)hydrazino]-1-ethyl-1H-pyrazolo[3,4-e]pyri 
dine-5-carboxylic acid, ethyl ester 
660 g. of 1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]-pyridine-5-carboxylic 
acid, ethyl ester (3 mol.) and 246 g. of 3-iminobutyronitrile (3 mol.) are 
refluxed with stirring in 3 liters of butanol for 12 hours. The solvent is 
distilled off and the residual 
4-[2-(2-cyano-1-methylethylidene)hydrazino]-1-ethyl-1H-pyrazolo[3,4-b]pyri 
dine-5-carboxylic acid, ethyl ester is recrystallized from alcohol, yield 
756 g. (80%); m.p. 190.degree. -191.degree.. 
b. 8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4', 
3':5,6]-pyrido[3,4-e]pyrimidin-5(8H)-one 
750 g. of 
4-[2-(2-cyano-1-methylethylidene)hydrazino]-1-ethyl-1H-pyrazolo[3,4-e]pyri 
dine-5-carboxylic acid, ethyl ester (2.8 mol.) are refluxed with stirring 
in 3 liters of acetic acid containing 50 g. of zinc chloride for 24 hours. 
The solution is cooled to room temperature and after the addition of about 
3 liters of cold water, 8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4', 
3':5,6]pyrido[3,4-e]pyrimidin-5 (8H)-one crystallizes and is filtered off. 
The purification of the compound is accomplished by dissolving in the 
theoretical amount of aqueous sodium hydroxide and acidifying the mixture 
with acetic acid. Yield 562 g. (75%); m.p. 285.degree. -286.degree. C. 
c. 2,4-dimethyl-8-ethyl-4H-pyrazolo[1,5-a]pyrazolo[4', 3': 
5,6]pyrido[3,4-e]pyrimidin-5(8H)-one 
2.7 g. of 
8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrimi 
din-5(8H)-one (0.01 mol.) are added to a suspension of 0.03 g. of sodium 
hydride in 50 ml. of diethylene glycol dimethyl ether at reflux 
temperature. The temperature is maintained for one hour and then lowered 
to 120.degree.. 2.8 g. of methyl iodide are added and heating is continued 
for 10 hours. The precipitated sodium iodide is filtered off, the solution 
evaporated to dryness and the residue recrystallized from ethyl-acetate, 
yield 1.9 g. (68%); m.p. 206.degree.-207.degree.. 
EXAMPLE 2 
4,8-Diethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e]pyr 
imidin-5(8H)-one 
By substituting ethyl iodide for the methyl iodide in the procedure of 
Example 1 c, 
4,8-dimethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]py 
rimidin-5(8H)-one is obtained in 71% yield, m.p. 178.degree.-180.degree. 
(ethyl acetate). 
EXAMPLE 3 
8-Ethyl-2-methyl-4-(3-methylbutyl)-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]py 
rido[3,4-e]pyrimidin-5(8H)-one 
By substituting 1-bromo-3-methylbutane for the methyl iodide in the 
procedure of Example 1 c, 
8-ethyl-2-methyl-4-(3-methylbutyl)-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]py 
rido-[4,3-e]pyrimidin-5(8H)-one is obtained, yield 59%, m.p. 
126.degree.-128.degree. (ethyl acetate). 
EXAMPLE 4 
4-[3-(Dimethylamino)propyl]-8-ethyl-2-methyl-4H-pyrazolo-[1,5-a]pyrazolo[4' 
,3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one 
5.4 g. of 
8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrimi 
din-5(8H)-one (0.02 mol.) are added to a solution of 1.5 g. of sodium 
methoxide in 50 ml. of diethylene glycoldimethyl-ether. The solution is 
refluxed with stirring for 30 minutes and then the temperature lowered to 
100.degree.. After the addition of 3 g. of dimethylaminopropyl chloride, 
the mixture is stirred for 24 hours. The inorganic precipitate is filtered 
off, the filtrate evaporated to dryness and the residue dissolved in 30 
ml. of water. The aqueous solution is brought to pH 10 with sodium 
hydroxide and extracted three times with 50 ml. portions of diethylether. 
The ether layers are combined, dried with sodium sulfate and the solvent 
is distilled off. The residue is crystallized with ether to obtain 2.8 g. 
(40%) of 
4-[3-(dimethylamino)-propyl]-8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4 
',3':5,6]-pyrido[3,4-e]pyrimidin-5(8H)-one, m.p. 65.degree.-68.degree. 
(propanol). Treatment of the product with acetic acid yields the acetate 
salt. 
EXAMPLE 5 
8-Ethyl-2-methyl-4-(2-morpholino)ethyl-4H-pyrazolo[1,5-a]-pyrazolo[4',3':5, 
6]pyrido[3,4-e]pyrimidin-5(8H)-one 
2.7 g. of 
8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrimi 
din-5(8H)-one (0.01 mol.) and 0.3 g. of sodium are refluxed for 1 hour in 
30 ml. of diethylene glycoldimethylether with stirring. The temperature is 
lowered to 90.degree. and 2 g. of 1-chloro-2-morpholinoethane are added 
and stirring is continued for 24 hours. The inorganic precipitate is 
filtered off, the solvent removed in vacuo and the crystalline product, 
8-ethyl-2-methyl-4-(2-morpholino)ethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5, 
6]pyrido-[3,4-e]pyrimidin-5(8H)-one is recrystallized from ethyl acetate, 
yield 3.1 g. (81%); m.p. 140.degree.-141.degree.. 
EXAMPLE 6 
8-Ethyl-2-methyl-4-(2-piperidino)ethyl-4H-pyrazolo[1,5-a]-pyrazolo[4',3':5, 
6]pyrido[3,4-e]pyrimidin-5(8H)-one 
By substituting for the dimethylaminopropyl chloride in Example 4 the 
equivalent amount of 1-chloro-2-piperidinoethane, 
8-ethyl-2-methyl-4-(2-piperidino)-ethyl-4H-pyrazolo-[1,5-a]pyrazolo[4',3': 
5,6]pyrido[3,4-e]pyrimidin-5(8H)-one is obtained, yield 62%; m.p. 
134.degree.-137.degree. (ethyl acetate). 
EXAMPLE 7 
4-[2-(Diethylamino)ethyl]-8-ethyl-2-methyl-4H-pyrazolo[1,5-a]-pyrazolo[4',3 
':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one 
By substituting for the 1-chloro-2-morpholinoethane in Example 5 the 
equivalent amount of 1-chloro-2-diethylaminoethane, 
4-[2-(diethylamino)ethyl]-8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3 
':5,6]pyrido[3,4-e]-pyrimidin-5(8H)-one is obtained, yield 63%; m.p. 
90.degree.-92.degree. (ethyl acetate). 
EXAMPLE 8 
2,4-Dimethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido-[3,4-e]pyrimidin-5 
(8H)-one 
By substituting an equivalent amount of 
4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, ethyl ester for 
the 1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, 
ethyl ester in the procedure of Example 1 a and continuing as in parts b 
and c, 
2-methyl-4H-pyrazolo-[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H 
)-one and 
2,4-dimethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e]pyrimidin- 
5(8H)-one are obtained. 
EXAMPLE 9 
4-Butyl-8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e 
]pyrimidin-5(8H)-one 
By substituting butyl iodide for the methyl iodide in the procedure of 
Example 1 c, 
4-butyl-8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e 
]pyrimidin-5(8H)-one is obtained. 
EXAMPLE 10 
2-Methyl-4-Phenylmethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e] 
pyrimidin-5(8H)-one 
By substituting the 
2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H 
)-one of Example 8 for the 
8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e]pyrimi 
din-5(8H)-one and benzyl iodide for the methyl iodide in the procedure of 
Example 1 c, 
2-methyl-4-phenylmethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido-[3,4-e 
]pyrimidin-5(8H)-one is obtained. 
EXAMPLE 11 
8-Ethyl-2-methyl-4-phenylethyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido 
[3,4-e]pyrimidin-5(8H)-one 
By substituting phenylethyl bromide for the methyl iodide in the procedure 
of Example 1 c 
8-ethyl-2-methyl-4-phenylethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido 
-[3,4-e]pyrimidin-5(8H)-one is obtained. 
EXAMPLE 12 
2,4,8,10-Tetramethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e]pyr 
imidin-5(8H)-one 
By substituting 
1,3-dimethyl-4-hydrazino-1H-pyrazolo-[3,4-b]pyridine-5-carboxylic acid, 
ethyl ester for the 
1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, ethyl 
ester in the procedure of Example 1 a and proceeding as in parts b and c, 
2,8,10-trimethyl-4H-pyrazolo[1,5-a]-pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimi 
din-5(8H)-one and 
2,4,8,10-tetramethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e]py 
rimidin-5(8H)-one are obtained. 
EXAMPLE 13 
4-Propionyl-2,3-diethyl-8-isopropyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-p 
yrido[3,4-e]pyrimidin-5(8H)-one 
By substituting 
1-isopropyl-4-hydrazino-1H-pyrazolo-[3,4-b]pyridine-5-carboxylic acid, 
ethyl ester for the 
1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, ethyl 
ester and 2-ethyl-3-iminopentanonitrile for the 3-iminobutyronitrile in 
the procedure of Example 1, a, proceeding as in part b and then 
substituting propionyl bromide for the methyl iodide in part c, 
2,3,8-triethyl-4H-pyrazolo-[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidi 
n-5(8H)-one and 
4-propionyl-2,3,8-triethyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3, 
4-e]pyrimidin-5(8H)-one, respectively, are obtained. 
EXAMPLE 14 
4-(4-Chlorobenzoyl)-10-ethyl-2-methyl-4H-pyrazolo[1,5-a]-pyrazolo[4',3':5,6 
]pyrido[3,4-e]pyrimidin-5(8H)-one 
By substituting 
4-hydrazino-3-ethyl-1H-pyrazolo-1H-pyrazolo[3,4-b]pyridine-5-carboxylic 
acid propyl ester for the 
1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, ethyl 
ester in the procedure of Example 1 a, proceeding as in part b and then 
substituting 4-chlorobenzoyl bromide for the methyl iodide in part c, 
10-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimi 
din-5(8H)-one and 
4-(4-chlorobenzoyl)-10-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6 
]pyrido[3,4-e]pyrimidin-5(8H)-one, respectively, are obtained. 
EXAMPLE 15 
4-Benzoyl-2-methyl-8-phenyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3, 
4-e]pyrimidin-5(8H)-one 
By substituting 
4-hydrazino-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, ethyl 
ester for the 1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic 
acid, ethyl ester in the procedure of Example 1 a, proceeding as in part b 
and substituting benzoyl iodide for the methyl iodide in part c, 
2-methyl-8-phenyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrim 
idin-5(8H)-one and 
4-benzoyl-2-methyl-8-phenyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido-[3 
,4-e]pyrimidin-5(8H)-one, respectively, are obtained. 
EXAMPLE 16 
8-Ethyl-2,4,6-trimethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e] 
pyrimidin-5(8H)-one 
By substituting 
1-ethyl-4-hydrazino-6-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, 
ethyl ester for the 
1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, ethyl 
ester in the procedure of Example 1, 
2,6-dimethyl-8-ethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e]py 
rimidin- 5(8H)-one and 
8-ethyl-2,4,6-trimethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e] 
pyrimidin-5(8H)-one, respectively, are obtained. 
EXAMPLE 17 
8-Benzyl-2-methyl-4-(3-methylbutyl)-4H-pyrazolo[1,5-a]-pyrazolo[4',3':5,6]p 
yrido[3,4-e]pyrimidin-5(8H)-one 
By substituting 
1-benzyl-4-hydrazino-1H-pyrazolo-[3,4-b]pyridine-5-carboxylic acid, ethyl 
ester for the 1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic 
acid, ethyl ester in the procedure of Example 1 a, proceeding as in part b 
and substituting 1-bromo-3-methylbutane for the methyl iodide in part c 
(as in Example 3), 
8-benzyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]-pyrim 
idin-5(8H)-one and 
8-benzyl-2-methyl-4-(3-methylbutyl)-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]p 
yrido[3,4-e]pyrimidin-5(8H)-one, respectively, are obtained. 
EXAMPLE 18 
4-Methyl-8-phenylethyl-3-propyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrid 
o[3,4-e]pyrimidin-5(8H)-one 
By substituting 
1-phenylethyl-4-hydrazino-1H-pyrazolo-[3,4-b]-pyridine-5-carboxylic acid, 
methyl ester for the 
1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, ethyl 
ester and 2-iminomethylpentanonitrile for the 3-iminobutyronitrile in the 
procedure of Example 1 a and proceeding as in parts b and c, 
3-propyl-8-phenylethyl-4H-pyrazolo[1,5-a]pyrazolo4',3':5,6]pyrido[3,4-e]py 
rimidin-5(8H)-one and 
4-methyl-8-phenylethyl-3-propyl-4H-pyrazolo-[1,5-a]pyrazolo[4',3':5,6]pyri 
do[3,4-e]pyrimidin-5(8H)-one, respectively, are obtained. 
EXAMPLE 19 
8-Ethyl-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4- 
e]pyrimidin-5(8H)-one 
By substituting 3-imino-3-phenylpropionitrile for the 3-iminobutyronitrile 
in the procedure of Example 1 a and proceeding as in parts b and c, 
8-ethyl-2-phenyl-4H-pyrazolo-[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimi 
din-5(8H)-one and 
8-ethyl-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4 
-e]pyrimidin-5(8H)-one, respectively, are obtained. 
EXAMPLE 20 
4-Methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]-pyrimidin-5(8H) 
-one 
By substituting 4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, 
ethyl ester for the 
1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, ethyl 
ester and the 3-iminopropionitrile for the 3-iminobutyronitrile in the 
procedure of Example 1 a and proceeding as in parts b and c, 
4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one and 
4-methyl-4H-pyrazolo8 1,5-A]-pyrimidin-5(8H)-one, respectively, are 
obtained. 
EXAMPLE 21 
8-Benzoyl-2-methyl-4-phenyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3, 
4-e]pyrimidin-5(8H)-one 
a. 
1-Furfuryl-2-methyl-4-phenyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[ 
3,4-e]pyrimidin-5(8H)-one 
By substituting 4-hydrazino-1-furfurylpyrazolo-[3,4-b]pyridine-5-carboxylic 
acid, ethyl ester for the 
1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, ethyl 
ester in Example 1 a and proceeding as in parts a and b, 
8-furfuryl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyr 
imidin-5(8H)-one is obtained. This compound is now processed as in Example 
1, part c, substituting bromobenzene for the methyl iodide. A small amount 
of copper catalyst is added to obtain 
1-furfuryl-2-methyl-4-phenyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido-[ 
3,4-e]pyrimidin-5(8H)-one. 
b. 
2-Methyl-4-phenyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e]pyrim 
idin-5(8H)-one 
0.01 mol. of 
1-furfuryl-2-methyl-4-phenyl-4H-pyrazolo-[1,5-a]pyrazolo[4',3':5,6]pyrido[ 
3,4-e]pyrimidin-5(8H)-one is heated in 50 ml. of diethyleneglycol dimethyl 
ether containing 0.01 mol. of selenium dioxide at reflux temperature with 
stirring for 2 hours. The mixture is filtered hot and evaporated to 
dryness. Crystalline 
2-methyl-4-phenyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimi 
din-5(8H)-one remains. 
c. 
8-Benzoyl-2-methyl-4-phenyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3 
,4-e]pyrimidin-5(8H)-one 
0.01 mol. of 
2-methyl-4-phenyl-4H-pyrazolo[1,5-a]-pyrazolo[4',3':5,6]pyrido[3,4-e]pyrim 
idin-5(8H)-one and 0.02 mol. of benzoyl chloride are stirred overnight in 
50 ml. of dry pyridine at room temperature. On addition of 50 ml. of 
water, 8-benzoyl-2-methyl-4-phenyl-4H-pyrazolo-[1,5-a]pyrazolo[4',3':5,6]p 
yrido[3,4-e]pyrimidin-5(8H)-one is filtered off. 
EXAMPLE 22 
2,4-Dimethyl-8-(4-methylbenzoyl)-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyri 
do[3,4-e]pyrimidin-5(8H)-one 
By substituting 
1-(4-methylbenzoyl)-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic 
acid, ethyl ester for the 
1-ethyl-4-hydrazino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid, ethyl 
ester in the procedure of Example 1 a and proceeding as in parts b and c, 
2-methyl-8-(4-methylbenzoyl)-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido-[ 
3,4-e]pyrimidin-5(8H)-one and 
2,4-dimethyl-8-(4-methylbenzoyl)-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyri 
do-[3,4-e]pyrimidin-5(8H)-one, respectively, are obtained. 
EXAMPLE 23 
4-(2-Aminoethyl)-2,6-dimethyl-8-ethyl-4H-pyrazolo[1,5-a]-pyrazolo[4',3':5,6 
]pyrido[3,4-e]pyrimidin-5(8H)-one 
By substituting the 
2,6-dimethyl-8-ethyl-4H-pyrazolo-[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]py 
rimidin-5(8H)-one obtained in Example 16 in the procedure of Example 4 and 
substituting 2-chloroethylamine for the dimethylaminopropyl chloride, 
4-(2-aminoethyl)-2,6-dimethyl-8-ethyl-4H-pyrazolo-[1,5-a]pyrazolo[4',3':5, 
6]pyrido[3,4-e]pyrimidin-5(8H)-one is obtained. 
The hydrochloride salt is obtained by treating the above product with 
ethanolic HCl. 
EXAMPLE 24 
4-(3-Ethoxypropyl)-8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]p 
yrido[3,4-e]pyrimidin-5(8H)-one 
By substituting 3-ethoxypropyl chloride for the dimethylaminopropyl 
chloride in the procedure of Example 4, 
4-(3-ethoxypropyl)-8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]p 
yrido[3,4-e]pyrimidin-5(8H)-one is obtained. 
EXAMPLE 25 
2-Methyl-4-methylthiomethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3, 
4-e]pyrimidin-5(8H)-one 
By substituting methylthiomethyl chloride for the dimethylaminopropyl 
chloride in the procedure of Example 4 and substituting the 
2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H 
)-one obtained in Example 8 for the 
8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e]pyrimi 
din-5(8H)-one, 
2-methyl-4-methylthiomethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3, 
4-e]pyrimidin-5(8H)-one is obtained. 
EXAMPLE 26 
8-Benzoyl-2-methyl-4-(p-methylphenyl)-4H-pyrazolo[1,5-a]-pyrazolo[4',3':5,6 
]pyrido[3,4-e]pyrimidin-5(8H)-one 
By substituting p-methylphenyl bromide for the bromobenzene in the 
procedure of Example 21a, and proceeding as in parts b and c, 
8-benzoyl-2-methyl-4-(p-methylphenyl)-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6 
]pyrido[3,4-e]pyrimidin-5(8H)-one is obtained. 
EXAMPLE 27 
4-[2-(Diethylamino)ethyl]-2,8,10-trimethyl-4H-pyrazolo[1,5-a]-pyrazolo[4',3 
':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one 
By substituting diethylaminoethyl chloride for the dimethylaminopropyl 
chloride and utilizing the 
2,8,10-trimethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido-[3,4-e]pyrimi 
din-5(8H)-one product of Example 12 instead of 
8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3'-5,6]-pyrido[3,4-e]pyrimi 
din-5(8H)-one in the procedure of Example 4, 
4-[2-(diethylamino)ethyl]-2,8,10-trimethyl-4H-pyrazolo[1,5-a]-pyrazolo[4', 
3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one is obtained. 
EXAMPLE 28 
4-Dimethylaminomethyl-2-methyl-8-phenyl-4H-pyrazolo[1,5-a]-pyrazolo[4',3':5 
,6]pyrido[3,4-e]pyrimidin-5(8H)-one 
By substituting dimethylaminomethyl chloride for the dimethylaminopropyl 
chloride in the procedure of Example 4 and utilizing 
2-methyl-8-phenyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrim 
idin-5(8H)-one product of Example 15 instead of 
8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrimi 
din-5(8H)-one, 
4-dimethylaminomethyl-2-methyl-8-phenyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3': 
5,6]pyrido[3,4-e]pyrimidin-5(8H)-one is obtained. 
EXAMPLE 29 
8-Ethyl-2-methyl-4-(2-thiamorpholino)ethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3' 
:5,6]pyrido[3,4-e]pyrimidin-5(8H)-one 
By substituting 1-chloro-2-thiamorpholinoethane for the 
1-chloro-2-morpholinoethane in the procedure of Example 5, 
8-ethyl-2-methyl-4-(2-thiamorpholino)ethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3 
':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one is obtained. 
EXAMPLE 30 
2-Methyl-4-(3-piperazino)propyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido 
[3,4-e]pyrimidin-5(8H)-one 
By substituting 3-piperazinopropyl chloride for the 
1-chloro-2-morpholinoethane in the procedure of Example 5 and utilizing 
the 2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrimidin- 
5(8H)-one product of Example 8, 
2-methyl-4-(3-piperazino)propyl-4H-pyrazolo[1,5-a]-pyrazolo[4',3':5,6]pyri 
do[3,4-e]pyrimidin-5(8H)-one is obtained. 
EXAMPLE 31 
The following ingredients are used to make 1,000 200 mg. tablets each 
containing 100 mg. of active ingredient: 
______________________________________ 
2,4-dimethyl-3-ethyl-4H-pyrazolo- 
[1,5-a]pyrazolo[4',3':5,6]pyrido- 
[3,4-e]pyrimidine-5(8H)-one 
100 gm. 
Polyvinyl pyrrolidone 7.5 gm. 
Lactose 20 gm. 
Magnesium stearate 3.5 gm. 
Corn starch 17.5 gm. 
Avicel (microcrystalline cellulose) 
51.5 gm. 
______________________________________ 
The medicament and lactose are thoroughly admixed. The polyvinyl 
pyrrolidone is dissolved in ethanol USP to make a 30% solution. This 
solution is used to granulate the mixture of medicament and lactose. The 
granulation is passed through a No. 16 screen and air dried. The dried 
granulation is then passed through a No. 20 screen. To the screened 
granulate are added the magnesium stearate, Avicel and the corn starch and 
the mixture is blended. The blend is then compressed into 200 mg. tablets 
on a standard concave punch. The tablets are then veneer coated with 
methyl cellulose in a spray pan.