CA1095907A - Meso-ionic didehydro derivatives of 1,7-dehydro-1- substituted -3h-pyrazolo [4,3-e]-1,2,4-triazolo [4,3-c]-pyrimidine-3-thiones and 3-ones - Google Patents

Meso-ionic didehydro derivatives of 1,7-dehydro-1- substituted -3h-pyrazolo [4,3-e]-1,2,4-triazolo [4,3-c]-pyrimidine-3-thiones and 3-ones

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Publication number
CA1095907A
CA1095907A CA309,665A CA309665A CA1095907A CA 1095907 A CA1095907 A CA 1095907A CA 309665 A CA309665 A CA 309665A CA 1095907 A CA1095907 A CA 1095907A
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Prior art keywords
lower alkyl
hydrogen
methyl
pyrazolo
pyrimidine
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French (fr)
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Uwe D. Treuner
Hermann Breuer
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ER Squibb and Sons LLC
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ER Squibb and Sons LLC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/38—Nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
    • C07D487/14—Ortho-condensed systems

Abstract

MT120b ABSTRACT

MESO-IONIC DIDEHYDRO DERIVATIVES OF 1,7-DEHYDRO-1-SUBSTITUTED-3H-PYRAZOLO[4,3-e]1,2,4-TRIAZOLO[4,3-c]-New 1,7-dihydro-1-substituted-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidine-3-thione and 3-one mesoionic didehydro derivatives which have the formula

Description

~ s~

MT120b MESO-IONIC DIDEHYDRO DERIVATIVES OF 1,7-DEHYDRO-l-SUBSTITUTED-3H-PYRAZOLO14,3-e]1,2,4-TRIAZOLO[4,3-c]-U.S. Patent No. 4,053,474 issued October 11, 1977 describes a group of 3-mercapto-7H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidines unsubstituted or lower alkyl substituted in the 7- and/or 9-positions as well as derivatives in which the sulfur in the 3-position bears various substituents. These previously described compounds are obtained, according to one method, from . a 1- and/or 3-unsubstituted or substituted 4-halo-pyrazolo[3,4-d]pyrimidine by sequential treatment with hydrazine and l,l-thiocarbonyldiimidazole. These compounds are of -the formula N N
~ 20 R ~ b ¦ ~N ~ SR3 R

.

: . ,.: ~
.
.~ .
: . . :
:~ ..

113~95~

wherein Rl and R2 each is hydrogen or lower alkyl; R3 is hy-drogen, a salt forming ion, -C-lower alkyl, lower alkyl or substituted lower alkyl wherein the lower alkyl substituent is hydroxy, cyano, phenyl, -C-O-lower alkyl, -~-R4, -N \ 5 or -CON \ ; R4 is lower alkyl or phenyl; R5 and R6 each 6 is hydrogen or lower alkyl or R5 and R6 together with the nitro-gen form one of the heterocyclic radicals pyrrolidino, piperi-dino, morpholino or piperazino; and R7 and R8 each is hydrogen or lower alkyl.
It has now been found that treatmen-t of the same unsubsti-tuted or substituted 4-halopyrazolo[3,4-d]pyrimidine with a monosubstituted hydrazine instead of hydrazine and then with l,l-thiocarbonyldiimidazole yields a 1,7-dihydro-1-substituted-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidine-3-thione meso-ionic didehydro derivative, an inner salt or meso-ionic ~orm in which the sulfur has a negative charge and a nitrogen has a positive charge, and the substituent on the original hydrazine reactant is now in the l-position. The same meso-ionic derivatives can also be obtained by utilizing carbon disulfide instead of l,l-thiocarbonyldiimidazole. Similarly, when l,l-carbonyldiimidazole is used instead of l,l-thiocar-bonyldiimidazole, the analogous oxygen containing products are obtained.
This invention relates to these new 1,7-dihydro-1-sub-stituted-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidine-3-thione or 3-one meso-ionic didehydro derivatives which have the general formula ~9~i911~
MT120b R - ~ X

Rl wherein Rl is hydrogen, lower alkyl, phenyl-lower alkyl, hydroxy-lower alkyl or cyclo-lower alkyl; R2 is hydrogen ~ or lower alkyl; R3 is lower alkyl, cyclo-lower alkyl or - hydroxy-lower alkyl; and X is sulfur or oxygen.
The lower alkyl groups represented by Rl, R2 and R3 are straight or branched chain aliphatic hydrocarbon radicals having up to seven carbon atoms. The Cl-C4 :~ members, and especially the Cl-C2 members are preferred.
Illustrative lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl and the like.
The hydroxy-lower alkyl groups are similar groups \ bearing a hydroxy substituent, preferably on the terminal carbon, e.g., hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl and the like. The same preferences as above apply.
Similarly, the phenyl-lower alkyl groups include a phenyl substituent on the alkyl chain, preferably on a terminal carbon. Again, those groups having one to four carbons in the alkyl chain, especially one or two as in phenylmethyl and phenylethyl, are preferred. The cyclo-loweralkyl groups similarly have up to seven carbons, preferably C5-C6.

:~

- . .
: ~;
-1~9~

M'l' 1 2 (~t-Preferred are compounds of Formula I wherein Rl and R3 each is lower alkyl, especially Cl-C4 alkyl, and R2 is hydrogen, most especially when X is sulfur. The examples illustrate particularly preferred em~odiments.
The products of this invention are synthesized from a 4-halopyrazolo[3,4-d]pyrimidine which has the formula hal wherein hal represents halogen, preferably chlorine.
lS The 4-halopyrazolo[3,4-d]pyrimidine i5 first made to react with a substituted hydrazine which has the formula (III) R3 NH NH2 in an alcohol like ethanol or propanol, preferably at about ambient temperature. This reaction results in an intermediate which has the formula (IV) R3-NI-NH2 R

~9~0~3 M~120b Whcn the intermediates of Formula IV is then made to react with l,l-thiocarbonyldiimidazole or with carbon disulfide in an inert organic reaction medium like dimethylformamide, ethyl aceta-te, diglyme or the like, preferably at an elevated temperature, e.g., about 80C., a product of ~ormula I wherein X is sulfur is obtained.
When l,l-carbonyldiimidazole is used instead, a product of Formula I wherein X is oxygen is obtained. I
When Rl is hydrogen or hydroxy-lower alkyl, the l-position or the hydroxy function, respectively, should be protected, e.g., as in U.S. Patent 3,828,057, prior to reaction with the diimidazole and finally deprotected.
The starting materials can be produced by the methods described in our aforementioned U.S.
15 3,828`,057, in U.S. Patents 3,720,674, issued March 13, 1973,; 3,732,225, issued May 8, 1973 and 3,873,556, issued March 25, 1975, and J. Org. Chem. 21, 1240 (1956).
The new compounds of this invention have anti-inflammatory properties and are useful as anti-inflammatory agents, for example, to reduce localinflammatory 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 1 tO 1OO mg/kg/day, preferably 3 to 20 mg/kg/day, in single or 2 to 4 diviaed æoses, as indicated by the Mouse Active Arthus Assay. The active substance is formulated in a composition such as tablet, capsule, solution or suspension containing up to about 500 mg per unit of dosage of a compound or mixture of compounds of Formula I. The material is cornpounded in conventional manner with a physiologically acceptable vehicle or carrier, excipient, binder, preservative, stabilizer, , ~; .

' ' ' ~ :.. ' ~

:. - . .. :.. .. - .. ..

109S907 MT120b flavor, etc., as called for by accepted pharmaceutical practice. Topical preparations containing about 0.01 to 3 percent by weight oE active substance in a conventional lotion, cream or ointment can also be used.
The following examples are illustrative of the invention and serve as models for the production of additional members by replacing with appropriately substituted reactants. All temperatures are in degrees Celsius.

. ~

~s~
MT120b Example 1 _ 1,7-Dihydro-1,7-dime-thyl-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3~c]pyrimidine-3-thione meso-ionic didehydro derivative A. l-methyl-4-carboethoxy-5-aminopyrazole 320 g of ethoxymethylene cyanoacetic acid ester are dissolved in 2 li-ters of absolute ethanol. 87 g of methyl-hydrazine are added dropwise with stirring. The temperature rises to 35. The reaction mixture is then refluxed for 12 hours. After distilling off the solvent, the solid residue is crystallized from a little methanol to obtain 162 g (95.8~) of 1-methyl-4-carboethoxy-5-aminopyrazole, m.p. 92-93.
B. 5-[(Ethoxymethylene)amino]-l-methyl-lH-pyrazole-4-carboxylic acid, e-thyl ester 84.6 g of 1-methyl-4-carboethoxy-5-aminopyrazole and 74.1 g of orthoformic acid triethyl ester are heated together until the splitting off of ethanol has ended.
The oily residue is distilled under oil pump vacuum to obtain 5-[(ethoxymethylene)amino]-1-methyl-lH-pyrazole-4-carboxylic acid, ethyl ester b.p. 98-102; m.p. 32-34 (yield 87~).
C. l-Methyl-1,5-dihydro-4H-pyrazolo[3,4-d]
pyrimidin-4-one 57 2 g of 5-[(ethoxymethylene)amino]-1-methyl-lH-pyrazole-4-carboxylic acid, ethyl ester are dissolved in 200 ml of ethanol, 4.4 g of ammonia are added and the reaction mixture is autoclaved at 60 for 40 hours.
After cooling, the mixture is filtered and the residual 30 1-methyl-1,5-dihydro-4H-pyrazolo-[3,4-d]pyrimidin-4-one is crystallized from dimethylformamide, m.p. 289-290 (yield 31 g - 80.7%).

~, .
:: -i9~)7 MT120b D. l-Methyl-4-chloropyrazolo[3,4-d]p~rimidine 80 g of 1-methyl~1,5-d:ihydro-4M-pyrazolo[3,4-d]-pyrimidin-4-one are added to 300 ml of phosphorus oxychloride and the mixture is refluxed. After distilling off the excess phosphorus oxychloride, the semi-solid residue is extracted with 3 X 100 ml of boiling benzene. The benzene extracts are combined and concentrated to half-volume, then added to petroleum ether. After standing 12 hours in the refrigerator, the precipitated 1-methyl-4-chloropyrazolo[3,4-d]pyrimidine is filtered under suction and recrystallized from cyclo-hexane to obtain 54 g of white crystals, m.p. 93-96 (yield 60.5%).
E. l-Methyl-4-(1-methylhydrazino)pyrazolo[3,4-d]-pyrimidine 81 g of 1-methyl-4-chloropyrazolo[3,4-d]pyrimidine are dissolved in 1 liter of n-propanol. 45 g of methyl-hydrazine are added dropwise at room temperature and stirred for 35 hours. The reaction mixture is filtered and the residual 1-methyl-4-(1-methylhydrazino)pyrazolo-[3,4-d]pyrimidine is recrystallized twice from dimethyl-formamide having added activated charcoal to obtain 67.2 g of white crystalline product, m.p. 214(yield 84~).
F. 1,7-Dihydro-1,7-dimethyl-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]p~vrimidine-3-thione meso-ionic didehvdro derivative ..
31 g of 1-methyl-4-(1-methylhydrazino)pyrazolo-[3,4-d]pyrimidine are dissolved in 100 ml of dimethyl-formamide and 30 g of l,l-thiocarbonyldiimidazole dissolved in 20 ml of dimethylformamide are added all at once. The reaction mixture is stirred for 12 hours at room temperature. The precipitate is filtered under suction and together with the residue, obtained by .

MT120b _9_ concentrating the filtrate, crystallized from dimethyl-formamide having added activated charcoal. 29 g of 1,7-dihydro-1,7-dimethyl-3H-pyrazolo[4,3-e]-1,2,4-triazolo-[4,3-c]pyrimidine-3-thione meso-ionic didehydro derivative are obtained as yellowish felt-like crystals, m.p. 7270 (yield 75.4%).
Example 2 1,7-Dihydro-l-methyl-7-methylethyl-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidine-3-thione meso-ionic didehydro derivative A. l-Methvlethyl-4-carboethoxy-5-aminopyrazole By substituting isopropylhydrazine for the methyl-hydrazine in the procedure of Example lA, l-methyl-ethyl-4-carboethoxy-5-aminopyrazole b.p. 0 05mm 123-127, is obtained.
B. 5-[(Ethoxymethylene)amino]-l-(methylethyl)-lH-pyrazole-4-carboxylic acid, ethyl ester sy substituting the product of part A in the procedure of Example l(B), 5-[(ethoxymethylene)aminol-1-(methylethyl)-lH-pyrazole-4-carboxylic acid, ethyl P o, 01 98-103 , is obtained C. l-Isopropyl-1,5-dihydro-4H-pyrazolo[3,4-d]-pyrimidine-4-one By substituting the product of part B in the procedure of Example l(C), l-isopropyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one, m.p. 193, is obtained.
D. 4-Chloro-l-methylethylpyrazolo[3,4-d]pyrimidine By substituting the product of part (C) in the procedure of Example l(D), 4-chloro-1-methylethylpyrazolo-[3,4-d]pyrimidine, m.p. 47-49, is obtained.

,,~
:
: : .
,- . . .: :
: . : :
.: ::

~1590~
MT120b E. l-(Meth~ethyl)-4-~1-meth~lh~razino)p~razolo-[3,4-d]p~rlmidine By substituting the product of part (D) in -the procedure of Example l(E), l-(methylethyl)~4-(1-methyl-hydrazino)pyrazolo[3,4-d]pyrimidine, m.p. 105-108, is obtained.
F. 1,7-Dihydro-l-methyl-7-methylethyl-3H-pyrazolo-[4,3-e]-1,2!4-triazolo[4,3-c]pyrimidine-3-thione meso-ionic didehydro derivative By substituting the product of part E in the procedure of Example l(F), 1,7-dihydro-1-methyl-7-methyl-ethyl-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidine-3-thione meso-ionic didehydro derivative, m.p. 290-292, is obtained.
Example 3 l-Butyl-1,7-dihydro-7-meth~l~-3H-pyrazolo[4~3-e]-l~2~4-triazolo[4,3-c]pyrimidine-3-thione meso-lonic didehydro derivative A. 4-(1-Butylhydra~ino)-l-methyl-lH-pyrazolo[3,4-d]-pyr-imidine By substituting butylhydrazine for the methyl-hydrazine in the procedure of Example l(E), 4-(1-butyl-hydrazino)-l-methyl-lH-pyrazolo[3,4-d]pyrimidine, m.p.
68-72, is obtained.
B. l-Butyl-1,7-dihydro-7-methyl-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidine-3-thione meso-ionic didehydro derivative By substituting the product of part A in the procedure of Example l(F), 1-butyl-1,7-dihydro-7-methyl-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidine-3-thione meso-ionic didehydro derivative, m.p. 272-275, is obtainecl.

.", : , , .

5~7 MT120b Example 4 1,7-Dihydro-l-methylethyl-7-methyl-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimicline-3-thione meso-ionic didehydro derivative A. 4~ Methylethylhyclrazino)-l-methyl-lH-pyrazolo-[3,4-d]p~rimidine By substituting isopropylhydrazine for the methyl-hydrazine in the procedure of Example l(E), 4-(1-methyl-ethylhydrazino)-l-methyl-lH-pyrazolo[3,4-d~pyrimidine, m.p. 57, is obtained.
s. 1,7-Dihydro-l-methylethyl-7-methyl-3H-pyraZolo-[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidine-3-thione meso-ionic didehydro derivative By substituting the product of part A in the procedure of Example l(F), 1,7-dihydro-1-methylethyl-7-methyl-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidine-3-thione meso-ionic didehydro derivative, m.p. 316-317, is obtained.

Example 5 1,7-Dih_dro-1,7-dimethyl-3H-pyrazolo[4,3-e]-1,2 _ triazolo[4,3-c]pyrimidine-3-thione meso-ionic didehydro derivative A. l-Methyl-4-(1-methylhydrazino)pyrazolo[3,4-d]-25 pyrimidine 1.7 g of methylhydrazine is dissolved in 30 ml ofethanol. 3.3 g of 4-chloro-1-methylpyrazolo[3,4-d]-pyrimidine is added portionwise. The mixture is refluxed for 30 minutes and then allowed to stand in the refrigerator overnigh~. The mixture is fil~ered and the product, l-methyl-4-(l~methylhydrazino)pyrazolo[3,4-d]-pyrimidine, is recrystallized from ethanol-methanol, m.p.
213-215 (yield 4.2 g.).

': -.

~0~
MT120b s. 1,7-Dihydro-1~7=dimethyl-3H-p~zolo[4,3-e]~
. _ 1,2,4-triazolo[4,3-c]pyrlmldine-3~thione meso-ionic didehydro derivative .
0.5 g of the product of part A is dissolved in 10 S ml of dimethylformamide. 0.22 g of carbon disulfide is added dropwise. The reaction mixture is then heated at 80 for two hours. The product, 1,7~dihydro-1,7-dimethyl-3H-pyrazolo[4,3-e]--1,2,4-triazolo[4,3-c]-pyrimidine-3-thione meso-ionic didehydro derivative, crystallized during the course of the reaction. The reaction mixture is cooled and filtered to obtain 0.5 g of the product, m.p. 300.

Exam~le 6 15 1,7-Dihydro-1,7-dimethyl-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,_3-c]pyrimidine-3-one meso~ionic didehydro derivative 1.7 g of 1-methyl-4-(1-methylhydrazino)pyrazolo-[3,4-d]pyrimidine and 1.62 g of l,l-carbonyldiimidazole in 20 ml of dimethylformamide are stirred at 80 for several minutes. The product, 1,7-dihydro-1,7-dimethyl-3H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidine-3-one-meso-ionic didehydro derivative,- precipitates in the form of felt-like needles. The product is recrystallized from dimethylformamide, m.p. 303-306 (yield 1.6 g).
The following additional compounds are produced by the procedure of Example 1 by forming the appropriately (Rl and R2) substituted aminopyrazole (according to parts A and B), and utilizing the appropriately (R3) substituted hydrazine (according to part E), (and Example 6 instead of Example ltF) for compounds wherein X is oxygen).

-' ' ~,~' ' ;

.. . .. . .
- , .
';

, . ,. ~ :

: .:
.
~' :

~ 7 Mrrl20b
2 ~ J + ~x -N N

Example Rl R2 R3 X

18 ~ -CH2- H C3H7- O

19 ~ 2 2 C4Hg- S
~ H CH3 O

21 ~ 2 5 22 ~ H CH O

23 C2H5 H ~ O

24 ~ H CH3 S

-:

~ .' ~: .: ~ , - : :,: ~ : . - , ' , :

Claims (24)

MT120b The embodiments of the invention in which an exclu-sive property or privilege is claimed are defined as follows:
1. A process for preparing a compound of the formula wherein R1 is hydrogen, lower alkyl, phenyl-lower alkyl, cyclo-lower alkyl or hydroxy-lower alkyl; R2 is hydrogen or lower alkyl; R3 is lower alkyl, cyclo-lower alkyl or hydroxy-lower alkyl; and X is sulfur or oxygen, characterized by reacting a compound of the formula II with a substituted hydrazine of the formula R3-NH-NH2 (III) to form an intermediate of the formula and then reacting said intermediate with 1,1-carbonyl-diimidazole to form a product wherein X is oxygen;
or reacting said intermediate with 1,1-thiocarbonyl-diimidazole or carbon disulfide to form a product wherein X is sulfur.

MT120b
2. A process as in claim 1 wherein R2 is hydrogen.
3. A process as in claim 1 wherein R1 is lower alkyl and R2 is hydrogen.
4. A process as in claim 1 wherein X is sulfur.
5. A process as in claim 1 wherein X is oxygen.
6. A process as in claim 1 wherein R1 and R3 each is lower alkyl, R2 is hydrogen and X is sulfur.
7. A process as in claim 1 wherein R1 and R3 each is lower alkyl, R2 is hydrogen and X is oxygen.
8. A process as in claim 1 wherein R1 and R3 each is methyl, R2 is hydrogen and X is sulfur.
9. A process as in claim 1 wherein R1 is methyl, R2 is hydrogen, R3 is methylethyl and X is sulfur.
10. A process as in claim 1 wherein R1 is methyl-ethyl, R2 is hydrogen, R3 is methyl and X is sulfur.
11. A process as in claim 1 wherein R1 is methyl, R2 is hydrogen, R3 is n-butyl and X is sulfur.
12. A process as in claim 1 wherein R1 and R3 each is methyl, R2 is hydrogen and X is oxygen.
13. A compound of the formula wherein R1 is hydrogen, lower alkyl, phenyl-lower alkyl, cyclo-lower alkyl or hydroxy-lower alkyl, R2 is hydrogen, or lower alkyl; R3 is lower alkyl, cyclo-lower alkyl or hydroxy-lower alkyl; and X is sulfur or oxygen whenever prepared by the process of claim 1.

MT120b
14. A compound as in claim 13 wherein R2 is hydrogen whenever prepared by the process of claim 2.
15. A compound as in claim 13 wherein R1 is lower alkyland R2 is hydrogen whenever prepared by the process of claim 3.
16. A compound as in claim 13 wherein X is sulfur, whenever prepared by the process of claim 4.
17. A compound as in claim 13 wherein X is oxygen, whenever prepared by the process of claim 5.
18. A compound as in claim 13 wherein R1 and R3 each is lower alkyl, R2 is hydrogen and X is sulfur, whenever prepared by the process of claim 6.
19. A compound as in claim 13 wherein R1 and R3 each is lower alkyl, R2 is hydrogen and X is oxygen, whenever prepared by the process of claim 7.
20. A compound as in claim 13 wherein R1 and R3 each is methyl, R2 is hydrogen and X is sulfur, whenever prepared by the process of claim 8.
21. A compound as in claim 13 wherein R1 is methyl, R2 is hydrogen, R3 is methylethyl and X is sulfur, whenever prepared by the process of claim 9.
22. A compound as in claim 13 wherein R1 is methyl-ethyl, R2 is hydrogen, R3 is methyl, and X is sulfur whenever prepared by the process of claim 10.
23. A compound as in claim 13 wherein R1 is methyl, R2 is hydrogen, R3 is n-butyl, and X is sulfur, whenever prepared by the process of claim 11.
24. A compound as in claim 13 wherein R1 and R3 each is methyl, R2 is hydrogen and X is oxygen whenever prepared by the process of claim 12.
CA309,665A 1977-09-13 1978-08-18 Meso-ionic didehydro derivatives of 1,7-dehydro-1- substituted -3h-pyrazolo [4,3-e]-1,2,4-triazolo [4,3-c]-pyrimidine-3-thiones and 3-ones Expired CA1095907A (en)

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US05/833,103 US4124764A (en) 1976-04-21 1977-09-13 Meso-ionic didehydro derivatives of 1,7-dehydro-1-substituted-3H-pyrazolo[4,]-1,2,4-triazolo[4,3-c]pyrimidine-3-thiones and 3-ones
US833,103 1986-02-25

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US4053474A (en) * 1976-04-21 1977-10-11 E. R. Squibb & Sons, Inc. Pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidine

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NO783086L (en) 1979-03-14
FR2402658A1 (en) 1979-04-06
GB2004278A (en) 1979-03-28
JPS5452098A (en) 1979-04-24
GB2004278B (en) 1982-01-13
DK402178A (en) 1979-03-14
NL7809035A (en) 1979-03-15
AU3914178A (en) 1980-02-28
IT7827559A0 (en) 1978-09-12
HU176023B (en) 1980-11-28
BE870456A (en) 1979-03-13
IT1099031B (en) 1985-09-18
DE2838029A1 (en) 1979-03-22
SE7809601L (en) 1979-03-14

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