TRIAZOLO(4,3-C)PYRIMIDINES AND TRIAZOLO(1,5-C)PYRIMIDINES SUBSTITUTED BY NITROGEN-CONTAINING HETEROCYCLIC RINGS

Abstract: 1,2,4-Triazolo[4,3-c]pyrimidines and 1,2,4-triazolo[1,5-­ c]pyrimidines substituted at the 5 or 7 positions through a nitrogen atom which is part of a heterocyclic ring have been found to have potent bronchodilator activity. Methods for inducing bronchodilation and pharmaceutical compositions are also disclosed.

Description: Triazolo[4,3-c]pyrimidines and Triazolo(l,5-cipyrimidines Substituted by Nitrogen-Containing Heterocyclic Rings Technical Field The present invention relates to triazolo[4,3-c]pyrimidines and triazolo[l,5-c]pyrimidines, and more specifically to l,2,4-triazolo[4,3-c)pyrimidines and l,2,4-triazolo[l,5-cjpyrimidines. The pharmacological use of the compounds of the invention as bronchodilators, and phannaceutical compositions comprising the compound are also within the scope of the invention. Background of the Invention Some 1,2,4-triazolo[4,3-c]pyrimidines and 1,2,4-triazolo[1,5-c]pyrimidines are known to the art. Certain 1,2,4-triazolo[4,3-c]pyrimidines and 1,2,4-triazolo[1,5-c]pyrimidines are disclosed as being bronchodilators in the patents discussed below, the 1,2,4-triazolo[1,5-6]pyrimidines being referred to therein as triazolo[2,3-c]pyrimidines: : United Kingdom Patent No. 859,287 discloses what were believed to be the compounds 3-amino-7-methyl-5-methyl thio-1,2,4-triazolol4,3-cpyrimidine and 3-amino-7-chloro 5-methyl-l,2,4-triazoloF4,3-c]pyrimidine. United Kingdom Patent No. 859,287 also discloses 2-amino-1,2,4-triazolo [1,5-c]pyrimidines which are substituted on the pyrimidine ring at the 5, 7 and 8 positions by certain combinations of substituents selected from hydrogen, alkyl, halogensubstituted alkyl, hydroxy-substituted alkyl, alkoxysubstituted alkyl, alkenyl, cycloalkyl, amino, alkylamino, dialkylamino, phenyl, alkylthio, alkoxy and halogen substituents. United Kingdom Patent No. 898,408 discloses 3-amino-1,2,4-triazolo[4,3-c)pyrimidines which are substituted on the pyrimidine ring at the 5-position by an alkyl, alkylthio, or amino subsi:ituent, at the 7-position by an alkyl, halogen-substituted alkyl or halogen substituent, and at the 8-position by hydrogen or an alkyl or alkenyl substituent. United Kingdom Patent No. 873,223 discloses 2-amino or 2-acetamido-1,2,4-triazolo[1,5-c]pyrimidines which are substituted on the pyrimidine ring at the 5, 7 and 8 positions by certain combinations of substituents selected from hydrogen, alkyl, halogen-substituted alkyl, alkoxy-substituted alkyl, alkenyl, cycloalkyl, alkylthio and halogen substituents. United Kingdom Patent No. 897,870 discloses 2-alkylamino-1,2,4-triazolotl,5-clpyrimidines, 2-dialkylamino-1,2,4-triazolo[1,5-c]pyrimidines, and 1,2,4-triazolo [1,5-clpyrimidines containing a piperidino or morpholino substituent bonded at the 2-position through the nitrogen atom, which compounds are substituted on the pyrimidine ring at the 5, 7 and 8 positions by certain combinations of substituents selected from hydrogen, alkyl, halogensubstituted alkyl, hydroxy-substituted alkyl, alkenyl and halogen substituents. The following related articles disclose the synthesis of certain 1,2,4-triazolo[4,3-c]pyrimidines and certain 1,2,4-triazolof1,5-c3pyrimidines as potential bronchodilators: G. W. Miller et al., J. Chem. Soc., 1963, 56-42, discloses 1,2,4-triazolo[4,3-clpyrimidines which are substituted at the 3-position by amino or amino substitutents, and on the pyrimidine ring by alkyl substituents or alkyl and alkenyl substituents This publication also discloses 2-amino- or 2-acetamido-1,2,4-triazolotl,5-cl- pyrimidines (referred to therein as triazolo[2,3-c]- pyrimidines) which are substituted on the pyrimidine ring by, for example, hydrogen and alkyl substituents. Certain of these latter-compounds are said to be bronchodilators. G. W. Miller et al., J. Chem. Soc., 1963, 3357, discloses the compound 3-hydroxy-7-methyl-5-n-propyl-1,2,4- triazolo[4,3-c]pyrimidine. This publication also discloses 1,2,4-triazolo[l,5-c]pyrimidines (referred to therein as triazolo[2,3-c]pyrimidines) which are substituted at the 2-position by hydroxy, halogen, alkoxy, amino or substituted amino substituents and on the pyrimidine ring by alkyl substituents, or alkyl and halogen- substituted alkyl substituents. W. Broadbent et al., J. Chem. Soc., 1963, 3369, discloses the compound 3-mercapto-7-methyl-5-n-propyl 1,2,4-triazolo[4,3-c]pyrimidine, This publication also discloses 1,2,4-triazolo[l,5-c]pyrimidines (referred to therein as triazolo[2,3-c]pyrimidines) which are substituted at the 2-position by a mercapto, alkylthio, alkylsulphonyl, or dialkylamino substituent, and on the pyrimidine ring by alkyl substituents or alkyl and halogensubstituted alkyl substituents. Still other 1,2,4-triazolo[4,3-c]pyrimidines and 1,2,4-triazolo[1,5-c]pyrimidines are disclosed in the following articles and patents. Shiho et al., Yakagaku Zasshi, 1956, 76, 804, discloses 1,2,4-triazolo[4,3-c]pyrimidines which are substituted at the 3-position by alkyl or phenyl substituents, and on the pyrimidine ring by both methyl and methoxy substituents. Temple et al., J. Org. Chem., 1963, 33, 530, discloses the compounds 8-amino-7-chloro-5-triazolo[4,3-c]- pyrimidine-3(2H)-one and 8-amino-7-chloro-s-triazolo [1,5-c|pyrimidine-2(3H)-one. D. J. Brown et al., Aust. J. Chem., 1978, 31, 2505, discloses 1,2,4-triazolo[4,3-c]pyrimidines which are substituted at the 3-position by hydrogen or alkyl substituents, and on the pyrimidine ring by hydrogen and/or alkyl substituents. This publication also discloses 1,2,4-triazolo[1,5-c]pyrimidines which are substituted at the 2-position by hydrogen or an alkyl substituent, and on the pyrimidine ring by hydrogen and/or alkyl substituents. D. J. Brown et al., Aust. J. Chem., 1979, 32, 1585, discloses 1,2,4-triazolot4,3-c]pyrimidines which are substituted at the 3-position by hydrogen or an alkyl substituent, and on the pyrimidine ring at the 5-position by a halogen, hydrazino, methylthio or methyl substituent, and at the 7-position by a methyl substituent. This publication also discloses 1,2,4-triazolo[l,5-c]pyrimidines which are substituted at the 2-position by hydrogen or an alkyl substituent, and on the pyrimidine ring at the 5-position by a halogen, hydrazino, alkyl or alkylthio substituent, and at the 7-position by an alkyl substituent. D. J. Brown et al., Aust. J. Chem., 19808 33, 1147, discloses pyrimidines which are substituted at the 2-position by hydrogen or an alkyl or phenyl substituent, and on the pyrimidine ring at the 5-position by halogen, dimethylaminomethyleneamino, hydroxyaminomethyleneamino or 5-acetoxyaminomethyleneamino, and at the 7-position by hydrogen or an alkyl substituent. U.S. Patent No. 4,269,980 discloses 5-, 7- and 8-(optionally substituted-phenyl)-1,2,4-triazolo [4,3-clpyrimidines which may be substituted at the 3-position by hydrogen or an alkyl substituent. This patent also discloses 5-, 7- and 8-(optionally substituted phenyl)-1,2,4-triazolo[l,5-c]pyrimidines which may be substituted at the 2-position by hydrogen or an alkyl substituent. These cempo-unds are all anxiolytic agents. Detailed Description of the Invention The present invention relates to 1,2,4-triazolot4,3-cJpyrimidines and 1,2,4-triazolo 11,5-clpyrimidines which are bronchodilators. The invention also relates to a method for inducing bronchodilation in a mammal using a l,2,4-triazolo[4,3-c]- pyrimidine or 1,2,4-triazololl,5,-clpyrimidine of the invention, and to pharmaceutical compositions comprising an effective amount of a 1,2,4-triazolo[4,3-clpyrimidine or 1,2,4-triazolo[1,5-c]pyrimidine of the invention and a pharmaceutically acceptable carrier. Specifically, the present invention relates to compounds of the formula IA EMI5.1 wherein R3 is hydrogen or lower alkyl; one of of R5 and R7 is the heterocyclic substituent EMI5.2 wherein X is oxygen, sulfur, sulfinyl, sulfonyl, methylene (-CH2-), imido (-NH-) or N-lower alkylimido EMI5.3 hen R5 is the above heterocyclic substituent, R7 is hydrogen or lower alkyl; when R7 is the above heterocyclic substituent, R5 is hydrogen, lower alkylthio, phenyl, or lower alkyl; and R8 is hydrogen, phenyl or lower alkyl; and pharmaceutically acceptable salts thereof. The present invention also relates to compounds of the formula IB EMI5.4 wherein R2 is hydrogen or lower alkyl; at least one of R5 and R7 is EMI5.5 wherein each X is independently oxygen, sulfur, sulfinyl, sulfonyl, methylene (-CH-), imido (-NH-) or N-lower alkylimido EMI6.1 and one of R5 and R7 may also be hydrogen, lower alkyl or phenyl; and R8 is hydrogen, lower alkyl or phenyl; and pharmaceutically acceptable salts thereof. "Lower alkyl" as used in the instant specification and claims designates straight or branched-chain alkyl groups containing one to about four carbon atoms. Preferred lower alkyl substituents are methyl and ethyl. The presently preferred compounds of Formulas IA and IB are those wherein X is sulfur or oxygen and R8 is hydrogen. These compounds are preferred because of their generally higher potency in protecting against histamineinduced contraction of isolated guinea pig tracheal tissue. This assay is discussed in greater detail below. Compounds of Formula IB are preferred because of their generally higher potency in protecting against histamine-induced contraction of isolated guinea pig tracheal tissue. Specific examples of preferred compounds of Formula IA which are active in the aforementioned assay at concentrations of 10 ug per ml or lower are: 3,5-bis(n-proyl)-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c] pyrimidine 5-ethyl-3-methyl-7-(4-thiomorpholino)-1 r 2,4-triazolof4,3-c]- pyrimidine 3-methyl-5-methylthio-8-phenyl-7-(4-thiomorpholino)-1,2,4 triazolot4,3-clpyrimidine 5-ethyl-3-isopropyl-7-(4-thiomorpholino)-1,2,4-trizolo [4,3-c] pyrimidine 3-ethyl-5-methyl-7-(4-thiomorpholino)-l ,2,4-triazolo- [4,3-c3pyrimidine 3 r 5-bis(n-propyl)-7-(4-morpholino)-1,2,4-triazolot4,3-cl- pyrimidine 3,5-diethyl-7-(1-piporidino)-1,2,4-triazolo[4,3-c]pyrimidine 2-ethyl-7-(4-morpholino)-5-n-propyl-1,2,4-triazolot4,3-c] pyrimidine 7-(4-morpholino)-5-methylthio-1,2,4-triazolo[4,3-c]pyrimidine 3-ethyl-5-n-propyl-7-(4-thiomorpholino)-l/2t4-tria [4,3-c]pyrimidine 7-(4-methyl-1-piperazino)-5-(n-propyl)-1,2,4-triazolo[4,3-c] pyrimidine 5-n-propyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c] pyrimidine 5-ethyl-7-(4-morpholino)-1,2,4-triazolo[4,3-c]pyrimidine 5-ethyl-3-methyl-7-(4-morpholino)-1,2,4-triazolo[4,3-cl- pyrimidine 3,5-diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c] pyrimid ine Specific examples of preferred compounds of Formula IB which are active in the aforementioned assay at concentrations of 5 ug per ml or lower are: : 2-methyl-5-(4-thiomorpholino)-1,2,4-triazolo[1,5-c]pyrimidine 2-ethyl-7-methyl-5-(4-thiomorpholino)-1,2,4-triazolo[1,5-c] pyrimidine 5,7-bis(4-morpholino]-1,2,4-triazolo[1,5-clpyrimidine 5-(4-morpholino)-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c] pyrimidine 2-ethyl-5-methyl-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c] pyrimidine 2-ethyl-5-methyl-7-(4-morpholino)-1,2,4-triazolo[1,5-c]- pyrimidine 2,5-diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c] pyrimidine 2-ethyl-7-(4-morpholino)-5-n-propyl-1,2,4-triazolo[1,5-c3- pyrimidine 7-(4-morpholino)-5-n-propyl-1,2,4-triazlo[1,5-c]pyrimidine 2-ethyl-5-n-propyl-7-(4-thiomorpholino)-l,2,4-triazolo [1,5-capyrimidine 5-n-propyl-7-(4-thiomorpholino)-1,2,4-triazolot1,5-cl- pyrimid ine 5-ethyl-7-(4-morpholino)-1,2,4-triazlo[1,5-c]pyrimidine 5-ethyl-2-methyl-7-(4-morpholino)-1,2,4-triazolol115-cl- pyrimidine 2,5-diethyl-7-(4-morpholino)-1,2,4-triazolo[1,5-clpyrimidine 2,5-diethyl-7- [4-(1-dioxothiomorpholino) 1-1,2,3-triazolo- [1,5-cl pyrimidine 2, 5-diethyl-7- [4- ( 1-oxothiomorpholino]-1,2,4-triozolofl,5-c]- pyrimidine The bronchodilator activity of the compounds of Formulas IA and IB was assessed by the measurement of effects on isolated tracheal spirals. This is a well-known and long established in vitro test method. The bronchodilator activity was determined according to the following procedure: Female guinea pigs were sacrificed and each trachea removed and cut into a spiral strip. This strip was mounted in a constant temperature (370C) muscle bath having a volume of approximately 15 ml. The bathing medium was Krebs-Henseleit solution. Movement of the tracheal strip was measured by means of an isometric transducer connected to an electric recorder. The bath was aerated with a mixture of 95% carbon dioxide and 5% oxygen. Contractions were induced in the strips by the addition of a suitable amount of histamine, acetylcholine or barium chloride. The amount of a given compound of Formula I (measured in ug/ml) required to provide greater than 75% relaxation of druginduced contraction is considered an effective concentration. For comparison, a well known standard bronchodilator, aminophylline, requires concentrations of 50 ug/ml versus histamine, 100 ug/ml versus acetylcholine and 10 ug/ml versus barium chloride to provide greater than 75% relaxation. The compounds of Formulas IA and IB which were most active in the in vitro test, including most of those listed above as preferred compounds, were tested in vivo in the guinea pig for oral activity in the so-called histamine aerosol method described in U.S. Patent 3,248,292. This test was modified slightly in that a 0.18 aqueous solution of histamine was used as the agent for inducing bronchial constriction. Oral doses were measured in mg/kg of body weight of the guinea pig. Some of the compounds of Formulas IA and IB were also found to have activity as inucolytics in an in vitro test for mucus production in which rats are orally dosed with compound prior to sacrifice. The trachea is then isolated and incubated with radiolabelled glucosamine and the effect of compounds o)w the incorporation of glucosamine into extracellular mucus is determined. An active compound reduces incorporation of glucosamine. Specific examples of preferred compounds which are active in this assay are: 5-methyl-7-thiomorpholino-1,2,4-triazolo[4,3-c]pyrimidine 7-Methyl-5-(4-morpholino)-l,2,4-triazolo[l,5-c]pyrimidine 2,7-Dimethyl-5-(4-methyl-l-piperazinyl)-l,2,4-triazolo- [1,5-c]pyrimidine 2,7-Dimethyl-5-(1-piperazinyl)-1,2,4-triazolo[1,5-c]- pyrimidine. The compounds of Formulas IA and IB may be administered to mammals in order to obtain bronchodilation. The compounds may be administered orally, parenterally or by inhalation. Preferably they are administered orally in tablets or capsules. The usual effective human dose will be in the ranye of 0.1 to 50 my/kg of body weight. Salts of compounds of Formulas IA and I8 are generally prepared by reaction with an equimolar amount of a relatively strong acid, preferably an inorganic acid such as hydrochloric, sulfuric or phosphoric acid, in a polar solvent. Isolation of the salt is facilitated by the addition of a solvent in which the salt is insoluble, an example of such a solvent is diethyl ether. The compounds of Formulas IA and IB, either as the free base or in the form of a pharmaceutically acceptable acid-addition salt, can be combined with conventional pharmaceutical diluents and carriers to Eorm such dosage forms as tablets, capsules, suspensions, solutions, suppositories and the like. The pharmaceutical carrier employed may be, for example, either a solid or liquid. Examples of solid carriers are lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, stearic acid, and the like. Liquid carriers include syrup, peanut oil, olive oil, water and the like. Similarly, the carrier or diluent can include a time delay material well known to the art, such as glyceryl monostearate or glyceryl distearate, these being employed alone or, for example, in combination with a wax. The compounds of Formulas IA and IB may be prepared by several synthetic routes. One such route is that shown in Scheme I below. This route is useful in preparing compounds wherein R5 is hydrogen, lower alkyl or phenyl; R7 is EMI10.1 and R2, R8 and X are as defined previously Each "alp" appearing in Scheme I is independently lower alkyl. Scheme I EMI11.1 EMI11.2 The reactions of steps (1), (2) and (3) have previously been reported for the preparation of compounds wherein R5 is hydrogen, methyl or ethyl and R8 is hydrogen or methyl. Thus, most of the compounds of formulas IV, V, and VI are known. Heterocyclic compounds of formulas VII, VIII and IX are novel. The known methods were used to carry out the reactions of steps (1), (2) and (3). Specifically, steps (1) and (2) were carried out as described in H. R. Henze et al., J. Org. Chem., 1952, 17, 1320 and H. R. Henze et al., J. Org. Chem., 1953, 18, 653, and step (3) was carried out as described in J. Chesterfield et al., J. Chem. Soc., 1955, 3478. Step (4) is carried out by reacting the optionally substituted 4-chloro-6-hydrazinopyrimidine of Formula VI with a heterocyclic amine of the formula VIA. The reactants are heated together without solvent or optionally (and preferably) in any solvent which does not participate in the reaction such as water. Two equivalents of the heterocyclic amine are preferably used. Alternatively, one equivalent of the heterocyclic amine may be replaced by an inorganic base to neutralize the hydrogen chloride, but lower yields are obtained. The reaction mixture is heated at a temperature up to or at its reflux temperature. A temperature is chosen which provides an adequate reaction rate. When water is used as the solvent, the temperature is generally in the range of 80 to 1100C. Good yields of the desired products are isolated by conventional methods such as filtration, extraction or chromatography. The novel intermediates of Formula VIII, which may also be prepared alternatively by following steps (5) and (6), are solids whose structural assignments are confirmed by infrared and nuclear magnetic resonance spectral analyses. Step (5) is carried out by reacting optionally substituted 4,6-dichloropyrimidines of Formula V with heterocyclic amines of the formula VIA. This reaction is carried out by heating the reactants without solvent, or preferably in any solvent which does not participate in the reaction. Two equivalents of the heterocyclic amine are preferably used, one to react with the chloropyrimidine and the other to neutralize the hydrogen chloride by-product. Alternatively, an inorganic base may be used to neutralize the hydrogen chloride by-product, but lower yields of the desired product are generally obtained. Heating is at a temperature up to and including the reflux temperature of the mixture. A temperature is chosen which provides an adequate reaction rate. If water is used as a solvent, the mixture is generally heated at its reflux temperature. Good yields of the desired product are isolated by conventional methods such as filtration, extraction or chromatography. The novel intermediates of Formula VII are solids. Structural assignments are confirmed by infrared and nuclear magnetic resonance spectral analyses. Step (6) is carried out by reacting the novel substituted 4-chloro-6-heterocyclicaminopyrimidine of Formula VII with hydrazine hydrate. The reaction is facile and is generally carried out at moderate temperatures, for example, from -200C to the reflux temperature of the solvent. The reaction is generally carried out by adding two equivalents of hydrazine hydrate to a solution of the pyrimidine. The solvent ill generally be a lower alkanol. The product is separated by conventional methods such as filtration, extraction or chromatography and is the same novel intermediate of Formula VIII obtained from step (4). Step (7) is carried out by reacting the intermediate of Formula VIII with an orthoester of formula VI IA. Such orthoesters are well known and readily available. Examples of suitable orthoesters include trimethyl orthoformate, triethyl orthoformate, triethyl orthoacetate, triethyl orthopropionate and the like. Since the orthoesters are liquids, it is convenient to mix the intermediates of Formula VIII with an excess oE orthoester and to heat the mixture at reflux until reaction is complete. Good yields of the desired solid compounds of Formula IA are obtained by conventional methods. In step (8), the 1,2,4-triazolo[4,3-c]pyrimidines of Formula IA are heated with an aqueous acid and thereby converted to the compounds of Formula IB wherein R5 is EMI14.1 The preferred aqueous acids are carboxylic acids such as formic acid, acetic acid and propionic acid. The reaction mixture is generally heated at reflux for up to several days. The desired product is isolated by conventional methods. The structural assignments are made based on infrared and nuclear magnetic resonance spectral analyses. The products are generally white crytalline solids. In some cases step (8) may be accomplished by continued heating of the reactants of step (7). This conversion occurs most readily when R5 is hydrogen, and is carried out by using diethyl sulfoxide as the solvent for the combined steps (7) and (8) as described in Example 104. Synthetic Scheme II shows a method for the preparation of compounds of Formulas IA and IB wherein both R5 and R7 are EMI14.2 wherein X is as defined previously and may be the same or different in the two heterocyclic amino groups; and R2 and R8 are as defined previously. Alk is as defined previously. Scheme II EMI15.1 Step (1) of Scheme II requires reaction of the 4-chloro-6-hydrazino-2-methylthiopyrimidine of Formula X with a heterocyclic amine of the Formula VIA. Generally the 4-chloo-6rhydrazino-2-methylthiopyrimidines of Formula X are known compounds or may be prepared by conventional methods. The reaction is generally conducted in an inert solvent, preferably water, optionally in the presence of an acid acceptor such as a tertiary organic amine, for example, triethylamine. The reaction is best carried out using two equivalents of the amine of Formula VIA, one to react with the 4-chloro- 6-hydrazino-2-methylthiopyr imid ine and one to react with the hydrochloric acid which results. The mixture is heated at reflux for several hours, then cooled. Usually the novel intermediate of Formula XI is obtained directly as a solid precipitate. Alternatively, it is obtained by extraction or chromatographic techniques. Step (2) of Scheme II is carried out by mixing the intermediate of Formula XI with an orthoester of Formula VII IA. The reaction is carried out as described for step (7) of Scheme I. The product obtained is a compound of Formula IA. The product of this step generally is a mixture which is separated by chromatography, preferably high pressure liquid chromatography, to provide the crystalline solid. Occasionally the desired isomer is obtained in such high purity that chromatographic separation is unnecessary. Step (3) of Scheme II requires heating of the compound of Formula IA in an excess of the heterocyclic amine of the Formula VIA, optionally in an inert solvent such as diglyme or dioxane. The reaction is generally carried out at the reflux temperature of the mixture. The product is isolated by conventional methods such as filtration, extraction or chromatography. An alternative scheme, used for preparing compounds of Formula IB wherein R5 is EMI16.1 wherein X is as defined previously; R7 is hydrogen or lower alkyl; and R2 and R8 are as defined previously, is shown in Scheme III. Scheme III EMI16.2 The compounds of Formula XIV are generally known or may be prepared by conventional methods. Known methods may be employed to vary substituents R2 and R7. The reaction of Scheme III occurs readily at moderate temperatures, for example from OOC up to the reflux temperature of the solvent. It is carried out either by adding the heterocyclic amine of Formula VIA to a solution of the intermediate of Formula XIV or vice versa. The solvent may be inert solvent, for example water or dioxane. The product of Formula IB prepared in Scheme III is obtained in good yields by conventional isolation methods. Synthetic Scheme IV illustrated below is a method for preparation of compounds of Formulas IA and IB wherein R2 and R7 are independently hydrogen or lower alkyl; R5 is EMI17.1 wherein X is as defined previously; and R8 is as defined previously. Scheme IV EMI17.2 The reaction of Scheme IV is similar to reaction of step (3) of Scheme II. The intermediates of Formula XV are known or may be prepared from known starting materials using known methods. The products of Scheme IV are prepared and isolated as described for that step. The following examples are provided to illustrate the methods used in the invention They are not intended to limit the invention. EXAMPLE 1. Preparation of 3,5-Diethyl-7-(4-methyl-l piperazino)-l,2,4-triazolo[4,3-c]pyrimidine and 2,7-Diethyl-5-(4-methyl-l-piperazinyl)-l ,2,4- triazolo[l,5--c]pyrimidine according to Scheme I. Part A. Preparation of 2-Ethyl-6-hydrazinyl-4-(4-methyl l-piperazinyl)pyrimidine according to Step (4) A mixture of 8.3 g (0.05 mole) of 4-chloro-2ethyl-6-hydrazinylpyrimidine and 11 g (0.10 mole) of l-methylpiperazine in 250 ml of water was heated at reflux for 16 hours and was then cooled and extracted with chloroform. The extracts were dried over magnesium sulfate and were then evaporated to provide 8.3 g (70%) of 2-ethyl-6-hydrazinyl-4-(4-methyl-1-piperazinyl)pyrimidine. Part B. Preparation of 3, 5-Diethyl-7- ( 4-methyl-l-piper- azinyl)-1,2,4-triazolo[4,3-c]pyrimidine according to Step (7) A mixture of 8.3 g (0.045 mole) of 2-ethyl-6hydrazinyl-4-(4-methyl-1-piperazinyl)pyrimidine and 75 ml of triethyl orthopropionate was heated at reflux for 48 hours. After cooling the mixture was evaporated in vacuo. Diethyl ether was added to the residue and the mixture was cooled. The precipitate was collected by filtration to provide 4.5 g (37%) of 3,5-diethyl-7-(4-methyl-l-piperazinyl)1,2,4-triazolo[4,3-c]pyrimidine. Recrystallization from ethyl acetate-hexane and then from ethyl acetate-cyclohexane provided a white -crystalline product, m.p. 128-13-1OC. Analysis for C14H22N6: Calculated: %C, 61.3; ZH, 8.1; ZN, 30.6; Found: %C, 59.8; %H, 8.2; %N, 30.1. The structural assignment was confirmed by nuclear magnetic resonance and infrared spectral analyses. Part C. Preparation of 2,5-Diethyl-7-(4-methyl-l-piper azinyl)-1,2,4-triazolo[1,5-c]pyrimidine according to step (8) A mixture of 3.3 g of 3,5-diethyl-7-(4-methyl-l- piperazinyl)-1,2,4-triazolo[4,3-capyrimidine and 50 ml of 97% formic acid was heated at reflux for 18 hours. The mixture was cooled and evaporated in vacuo to provide a residue which was dilutes with 100 ml of water and carefully neutralized with sodium bicarbonate. The solution was extracted with chloroform. The extracts were dried and then concentrated to provide an oil which solidified and was collected by filtration, washed with water and dried. Recrystallization from hexane provided off-white crystalline solid 2,5-diethyl-7-(4-methyl-l-piper azinyl)-l,2,4-triazolo[l,5-c] pyrimidine, m.p. 87-880C. Analysis: Calculated for C14H22N6: %C, 61.3; ZH, 8.1; %N, 30.6; Found: %C, 60.6; %H, 8.1, %N, 30.6. The structural assignment was confirmed by infrared and nuclear magnetic resonance spectral analyses. EXAMPLES 2-21. Using the method of Part A, Example 1, the indicated intermediate amines of Formula VIA were reacted with the indicated known 4-chloro-2-alkyl-6-hydrazinylpyrimidines of Formula VI to provide the novel intermediates of Formula VIII (Table I). TABLE I EMI20.1 <SEP> Pyrimidine <tb> <SEP> Amine <SEP> Intermediate <SEP> Melting <SEP> Point <tb> Example <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VI <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VIII <SEP> (in C) <tb> <SEP> 2 <SEP> # <SEP> # <SEP> # <SEP> none <SEP> taken <tb> <SEP> (yield <SEP> 66%) <tb> <SEP> 3 <SEP> # <SEP> # <SEP> 158-160 <tb> <SEP> (yield <SEP> 94.5%) <tb> <SEP> 4 <SEP> # <SEP> # <SEP> 129-133 <tb> <SEP> (yield <SEP> 75%) <tb> Table I (continued) EMI21.1 <SEP> Pyrimidine <tb> <SEP> Amine <SEP> Intermediate <SEP> Melting <SEP> Point <tb> Example <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VI <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VIII <SEP> (in C) <tb> <SEP> 5 <SEP> # <SEP> # <SEP> # <SEP> 112-115 <tb> <SEP> 6 <SEP> # <SEP> # <SEP> # <SEP> none <SEP> taken <tb> <SEP> (yield <SEP> 84%) <tb> <SEP> 7 <SEP> # <SEP> # <SEP> # <SEP> 144-146 <tb> <SEP> (yield <SEP> 71%) <tb> Table I (Continued) EMI22.1 <SEP> Pyrimidine <tb> <SEP> Amine <SEP> Intermediate <SEP> Melting <SEP> Point <tb> Example <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VI <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VIII <SEP> (in C) <tb> <SEP> 8 <SEP> # <SEP> # <SEP> # <SEP> none <SEP> taken <tb> <SEP> (yield <SEP> 85%) <tb> <SEP> 9 <SEP> # <SEP> # <SEP> # <SEP> none <SEP> taken <tb> <SEP> (yield <SEP> 68%) <tb> <SEP> 10 <SEP> # <SEP> # <SEP> # <SEP> 183-185 <tb> Table I (Continued) EMI23.1 <SEP> Pyrimidine <tb> <SEP> Amine <SEP> Intermediate <SEP> Melting <SEP> Point <tb> Example <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VI <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VIII <SEP> (in C) <tb> <SEP> 11 <SEP> # <SEP> # <SEP> # <SEP> none <SEP> taken <tb> <SEP> (yield <SEP> 66%) <tb> <SEP> 12 <SEP> # <SEP> # <SEP> # <SEP> 203-204 <tb> <SEP> 13 <SEP> # <SEP> # <SEP> # <SEP> 174-177 <tb> Table 1 (Continued) EMI24.1 <SEP> Pyrimidine <tb> <SEP> Amine <SEP> Intermediate <SEP> Melting <SEP> Point <tb> Example <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VI <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VIII <SEP> (in C) <tb> <SEP> 14 <SEP> # <SEP> # <SEP> # <SEP> 155-157 <tb> <SEP> 15 <SEP> # <SEP> # <SEP> # <SEP> 147-149 <tb> <SEP> 16 <SEP> # <SEP> # <SEP> # <SEP> 122-123 <tb> Table I (Continued) EMI25.1 <SEP> Pyrimidine <tb> <SEP> Amine <SEP> Intermediate <SEP> Melting <SEP> Point <tb> Example <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VI <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VIII <SEP> (in C) <tb> <SEP> 17 <SEP> # <SEP> # <SEP> # <SEP> 124-126 <tb> <SEP> 18 <SEP> # <SEP> # <SEP> # <SEP> none-taken <tb> <SEP> 19 <SEP> # <SEP> # <SEP> # <SEP> none-taken <tb> Table I (Continued) EMI26.1 <SEP> Pyrimidine <tb> <SEP> Amine <SEP> Intermediate <SEP> Melting <SEP> Point <tb> Example <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VI <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VIII <SEP> (in C) <tb> <SEP> 20 <SEP> # <SEP> # <SEP> # <SEP> (oil) <tb> <SEP> 21 <SEP> # <SEP> # <SEP> # <SEP> (oil) <tb> Examples 22-59 Using the method of Part B, Example 1, the indicated intermediates of Formula VIII were reacted with the indicated trialkyl orthoesters to provide the novel compounds of Formula IA (Table II). Table II Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Ex. of Formula VIII Ortho Ester Compound of Formula IA (m.p. in C) R5 R8 X R2 R5 R8 X 22 CH3 H SO2 triethyl H CH3 H SO2 44.9; 4.9; 26.2 orthoformate 44.9; 4.9; 26.3 (299-300) 23 CH3 H SO2 triethyl CH3 CH3 H SO2 47.0; 5.4; 25.0 orthoacetate 47.1; 5.4; 24.9 (307-308) 24 CH2CH2CH3 H O triethyl H CH2CH2CH3 H O 58.3; 6.9; 28.3 orthoformate 58.2; 7.0; 28.4 (200-202) 25 CH2CH2CH3 H O triethyl CH2CH3 CH2CH2CH3 H O 61.1; 7.7; 25.4 orthopropionate 60.9; 7.9; 25.7 (179-181) 26 CH2CH2CHE H S triethyl H CH2CH2CH3 H S 54.7; 6.5; 26.2 orthoformate 54.6; 6.5; 26.9 (208-209) Table II (continued) Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Ex. of Formula VIII Ortho Ester Compound of Formula IA (m.p. in C) R5 R8 X R2 R5 R8 X 27 CH2CH2CH3 H S triethyl CH2CH3 CH2CH2CH3 H S 57.7; 7.3; 24.0 orthopropionate 57.7; 7.5; 24.4 (143-144) 28 CH2CH3 H CH2 triethyl CH2CH3 CH2CH2CH3 H CH2 (as H2SO4 salt): orthopropionate 48.5; 6.8; 18.9 48.4; 7.0; 19.0 (190-192) 29 CH3 H S triethyl H CH3 H S 51.0; 5.6; 29.8 orthoformate 51.0; 5.5; 29.6 (234-237) 30 CH2CH3 H CH2 triethyl CH2CH3 CH2CH3 H CH2 64.8; 8.2; 27.0 orthopropionate 65.1; 8.3; 27.2 (120-122) Table II (continued) Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Ex. of Formula VIII Ortho Ester Compound of Formula IA (m.p. in C) R5 R8 X R2 R5 R8 X 31 CH2CH3 H S triethyl CH2CH3 CH2CH3 H S 56.3; 6.9; 25.2 orthopropionate 56.1; 7.2; 25.5 (149-150) 32 CH2CH3 H S triethyl CH3 CH2CH3 H S 54.7; 6.5; 26.6 orthoacetate 54.4; 6.7; 26.7 (168-170) 33 CH2CH3 H S triethyl H CH2CH3 H S 53.0; 6.0; 28.1 orthoformate 52.6; 6.2; 28.2 (243-245) 34 CH2CH3 H O triethyl CH3 CH2CH2CH3 H O 58.3; 6.9; 28.1 orthoacetate 58.2; 7.0; 28.5 (200-203) Table II (continued) Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Ex. of Formula VIII Ortho Ester Compound of Formula IA (m.p. in C) R5 R8 X R2 R5 R8 X 35 CH2CH3 H O triethyl CH2CH3 CH2CH3 H O 59.7; 7.3; 26.8 orthopropionate 59.6; 7.4; 27.0 (173-174) 36 CH2CH3 H O triethyl H CH2CH3 H O 56.6; 6.5; 30.0 orthoformate 56.6; 6.4; 30.3 (223-224) 37 CH3 H O triethyl H CH3 H O 54.8; 6.0; 31.9 orthoformate 54.7; 6.0; 31.4 (208-210) 38 CH3 H O triethyl CH3 CH3 H O 56.6; 6.5; 30.0 orthoacetate 56.7; 6.3; 30.3 (171-173) Table II (continued) Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Ex. of Formula VIII Ortho Ester Compound of Formula IA (m.p. in C) R5 R8 X R2 R5 R8 X 39 CH3 H O triethyl CH2CH3 CH3 H O 58.3; 6.9; 28.3 orthopropionate 57.9; 7.0; 28.3 (169-172) 40 CH3 H S triethyl CH3 CH3 H S 53.0; 6.0; 28.1 orthoacetate 53.1; 6.3; 28.3 (223-225) 41 CH3 H S triethyl CH2CH3 CH3 H S 54.8; 6.5; 26.6 orthopropionate 54.4; 6.7; 26.8 (161-163) 42 CH3 CH3 S triethyl H CH3 CH3 S 56.0; 6.0; 28.1 orthoformate 53.2; 6.3; 28.4 (182-184) Table II (continued) Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Ex. of Formula VIII Ortho Ester Compound of Formula IA (m.p. in C) R5 R8 X R2 R5 R8 X 43 CH3 CH3 S triethyl CH3 CH3 CH3 S 54.7; 6.5; 26.6 orthoacetate 54.4; 6.6; 26.9 (184-185) 44 CH3 CH3 S triethyl CH2CH3 CH3 CH3 S 56.3; 6.9; 25.2 orthopropionate 56.4; 7.1; 25.1 (129-130) 45 CH3 CH3 SO2 triethyl H CH3 CH3 SO2 46.9; 5.4; 24.9 orthoformate 47.0; 5.3; 25.2 (234-236) 46 CH2CH3 H S triethyl CH2CH2CH3 CH2CH3 H S 57.7; 7.3; 24.0 orthobutyrate 57.6; 7.5; 24.2 (163-165) Table II (continued) Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Ex. of Formula VIII Ortho Ester Compound of Formula IA (m.p. in C) R5 R8 X R2 R5 R8 X 47 CH2CH3 H O triethyl CH2CH2CH3 CH2CH3 H O 61.1; 7.7; 25.4 orthobutyrate 61.0; 7.9; 25.8 (164-166) 48 CH2CH3 H O triethyl CH(CH3)2 CH2CH3 H O 61.1; 7.7; 25.4 orthoisobutyrate 61.0; 7.7; 25.3 (136-137) 49 CH2CH3 H S triethyl CH(CH3)2 CH2CH3 H O 57.7; 7.3; 24.0 orthoisobutyrate 57.8; 7.3; 24.2 (143-144) 50 CH2CH2CH3 H S triethyl CH2CH2CH3 CH2CH2CH3 H S 59.0; 7.6; 22.9 orthobutyrate 59.0; 7.5; 23.1 (134-135) Table II (continued) Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Ex. of Formula VIII Ortho Ester Compound of Formula IA (m.p. in C) R5 R8 X R2 R5 R8 X 51 CH2CH2CH3 H O triethyl CH2CH2CH3 CH2CH2CH3 H O 62.3; 8.0; 24.2 orthobutyrate 62.2; 8.1; 24.1 (139-140) 52 CH2CH2CH3 H S triethyl CH(CH3)2 CH2CH2CH3 H S 59.0; 7.6; 22.9 orthoisobutyrate 59.1; 7.7; 23.0 (134-136) 53 CH2CH2CH3 H O triethyl CH(CH3)2 CH2CH2CH3 H O 62.3; 8.0; 24.2 orthoisobutyrate 62.4; 8.1; 24.6 (116-117) 54 CH2(CH3)2 H O triethyl H CH2(CH3)2 H O (as H2SO4 Salt): orthoformate 41.7; 5.5; 20.3 41.6; 5.7; 20.6 (177-178) Table II (continued) Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Ex. of Formula VIII Ortho Ester Compound of Formula IA (m.p. in C) R5 R8 X R2 R5 R8 X 55 CH(CH3)2 H O triethyl CH2CH3 CH(CH3)2 H O (as H2SO4 Salt): orthopropionate 45.0; 6.2; 18.8 44.9; 6.3; 19.0 (167-168) 56 CH(CH3)2 H O triethyl CHCH2CH3 CH(CH3)2 H O (as H2SO4 Salt): orthobutyrate 46.5; 6.5; 18.1 46.2; 6.5; 18.3 (162-163) 57 CH(CH3)2 H S triethyl CH3 CH(CH3)2 H S (as H2SO4 Salt): orthoacetate 41.6; 5.6; 18.7 41.6; 5.8; 18.8 (170-172) Table II (continued) Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Ex. of Formula VIII Ortho Ester Compound of Formula IA (m.p. in C) R5 R8 X R2 R5 R8 X 58 CH(CH3)2 H S triethyl CH2CH3 CH(CH3)2 H S (as H2SO4 Salt): orthopropionate 43.2; 6.0; 18.0 43.1; 6.1; 18.2 (174-175) 59 CH(CH3)2 H O triethyl H CH(CH3)2 H O (as H2SO4 Salt): orthoformate 41.7; 5.5; 20.3 41.6; 5.7; 20.6 (177-178) Examples 60-96 Using the method of Part C, Example 1, the indicated compounds of Formula IA were heated with formic acid to provide the indicated compounds of Formula IB (Table III). Table III Compound of Formula IA; product of Formula IB Product of Formula IB Ex. Calculated: %C; %H; %N No. R2 Rk g X Found: %C; %H; %N 60 CH2CH3 CH2CH3 H CH2 64.8; 8.2; 27.0 65.1; 8.3; 27.0 m.p. 90-92"C 61 CH2CH3 CH2CH3 H S 56.3; 6.9; 25.2 56.1; 7.1; 25.0 m.p. 119-1200C 62 CH3 CH2CH3 H S 54.7; 6.5; 26.6 54.8; 6.8; 26.5 m.p. 164-1650C 63 H CH2CH3 H S 53.0; 6.0; 28.1 52.9; 6.3; 28.4 m.p. 228-2300C 64 CH3 CH2CH3 H 0 58.3; 6.9; 28.3 58.3; 7.0; 28.3 m.p. 159-1600C 65 CH2CH3 CH2CH3 H 0 59.7; 7.3; 26.8 59.7; 7.3; 26.9 m.p. 118-1190C 66 H CH2CH3 H 0 56.6; 6.5; 30.0 56.8; 6.5; 30.1 m.p. 168-1700C Table III (continued) Compound of Formula IA; Product of Formula IB Product of Formula IB Ex. Calculated: %C; %H; %N No. R2 R5 R8 X Found: %C, %H, %N 67 H CH3 H O2S 44.9; 4.9; 26.2 44.9; 4.9; 26.2 m.p. 251-2530C 68 CH3 CH3 H 02S 47.0; 5.4; 25.0 46.8; 5.4; 24.4 m.p. 229-2330C 69 H (CH2)2CH3 H 0 58.3; 6.9; 28.3 58.5; 7.0; 28.6 m.p. 153-155 C 70 CH2CH3 (CH2)2CH3 H 0 61.1; 7.7; 25.4 61.2; 7.7; 25.6 m.p. 130-1310C 71 H (CH2)2CH3 H S 54.7; 6.5; 26.6 54.9; 6.5; 26.9 m.p. 145-150 C 72 CH2CH3 (CH2)2CH3 H S 57.7; 7.3; 24.0 57.6; 7.3; 24.2 m.p. lOl-l030C 73 CH2CH3 (CH2)2CH3 H CH2 65.9; 8.5; 25.6 65.8; 8,6; 25.8 m.p. 60-62 C Table III (continued) Compound of Formula IA; Product of Formula IB Product of Formula IB Ex. Calculated: %C; %H; %N No. R2 R5 R8 X Found: %C; %H; %N 74 H CH3 H S 51.0; 5.5; 29.8 51.0; 5.7; 30.2 m.p. 154-1560C 75 H CH3 H 0 54.8; 6.0; 31.9 54.7; 5.8; 32.4 m.p. 159-161.50C 76 CH3 CH3 H 0 56.5; 6.5; 30.0 56.7; 6.6; 30.6 m.p. 182-1830C 77 CH2CH3 CH3 H 0 58.3; 6.9; 28.3 58.3; 7.0; 28.7 m.p. 146-147 C 78 CH3 CH3 H S 53.0; 6.0; 28.1 52.7; 6.1; 28.0 m.p. 170-1720C 79 CH2CH3 CH3 H S 54.7; 6.5; 26.7 54.6; 6.7; 27.1 m.p. 124-1250C 80 H CH3 CH3 S 53.0; 6.0; 28.1 52.9; 6.2; 28.4 m.p. 150-152 C Table III (continued) Coopond of Formula IA; Product of Formula IB Product of Formula IB Ex. Calculated: %C; %H; %N No. R2 R5 X Found: %C; %H; %N 81 CH3 CH3 CH3 S 54.7; 6.5; 26.2 54.8; 6.5; 26.6 m.p. 128-130 C 82 CH2CH3 CH3 CH3 S 56.3; 6.9; 25.2 56.3; 6.9; 25.4 m.p. 80-81 C 83 H CH3 CH3 O2S 46.9; 5.4; 24.9 46.9; 5.3; 25.1 m.p. 219-224 C 84 CH(CH3)2 CH2CH3 H S (as H2504 Salt): 43.7; 6.0; 18.0 43.1; 6.0; 18.4 m.p. 193-194 C 85 CH(CH3)2 CH2CH3 H O (as H2S04 Salt): 45.0; 6.2; 18.8 44.9; 6.3; 19.1 m.p. l89-1900C 86 (CH2)2CH3 CH2CH3 H O (as H2S04 Salt): 45.0; 6.2; 18.8 44.9; 6.3; 19.1 m.p. 170-172 C Table III (continued) Compound of Formula IA; Product of Formula IB Product of Formula IB Ex. Calculated: %C; %H; %N No. R2 R5 R8 X Found: %C, %H, %N 87 (CH2)2CH3 CH2CH3 H S (as H2SO4 Salt): 43.2; 6.0; 18.0 43.0; 6.1; 18.3 m.p. 152-153 C 88 (CH2)2CH3 CH3(CH2)2 H S (as H2SO4 Salt): 44.6; 6.2; 17.4 44.7; 6.4; 17.5 m.p. 143-145 C 89 (CH2)2CH3 (CH2)2CH3 H O (as H2SO4 Salt): 46.5; 6.5; 18.1 46.6; 6.7; 18.4 m.p. 169-171 C 90 CH(CH3)2 (CH2)2CH3 H S (as H2S04 Salt): 44.6; 6.2; 17.4 44.8; 6.4; 17.6 m.p. 172-173 C 91 CH(CH3)2 CH3(CH2)2 H O (as H2S04 Salt): 46.5; 6.5; 18.1 46.4; 6.7; 18.3 m.p. 156-157 C 92 CH2CH3 CH(CH3)2 H 0 61.1; 7.7; 25.4 61.0; 7.9; 25.9 m.p. 128-1290C Table III (continued) Compound of Formula IA; Product of Formula IB ¯ Product of Formula IB Ex. Calculated: %C; %H; %N No. R2 R5 R8 X Found: %C, %H, %N 93 (CH2)2CH3 CH(CH3)2 H 0 62.3; 8.0; 24.2 61.3; 8.1; 24.0 m.p. 85-86 C 94 CH3 CH(CH3)2 H S 56.3; 6.9; 25.3 56.1; 6.9; 25,8 m.p. 170-172 C 95 CH2CH3 (CH3)2CH H S 57.7; 7.3; 24.0 57.3; 7.1; 24.3 m.p. 142-1430C 96 H CH(CH3)2 H O (as H2S04 Salt): 41.7; 5.5; 20.3 41.0; 5.2; 20.3 m.p. 179-1820C EXAMPLE 97 Preparation of 2-n-Propyl-7-(4-thiomorpholino) 1,2,4-triazolo[l,5-c]pyrimidine A mixture of 8.00 g (37.9 irirnole) of 4-hydrazino6-(4-thiomorpholino)pyrimidine and 20 ml of trimethyl ortho-n-butyrate was heated at its reflux temperature for about 60 hours, cooled, and the solid was isolated by filtration. The product was washed with diethyl ether, then recrystallized twice from a benzene-hexane mixture accompanied by treatment with decolorizing charcoal to provide off-white 2-n-propyl-7-(4-thiomorpholino) 1,2,4-triazolo[1,5-c]pyrimidine, m.p. 137-1380C. Most (4.6 g, 17.5 mmole) of this product was dissolved in 100 ml of ethanol and 1.75 g (17.1 mmole) of sulfuric acid was added. The solution was diluted to 300 ml with diethyl ether and allowed two stand for two hours. The precipitate was collected by filtration, washed with diethyl ether and dried to provide the dihydrogen sulfate salt, m.p. 134-1370C. Analysis: Calculated for Cl2Hl7N5S*H2SO4: %C, 39.9; %H, 5.3; %N, 19.4; Found: %C, 39.5; ZH, 5.2; %N, 19.5. The structural assignment was confirmed by infrared spectral analysis. Examples 98-103 Using the method of Example 97, the indicated intermediates of Formula VIII were reacted with the indicated orthoesters to provide the indicated compounds of Formula 113 (Table IV). Table IV Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Example of Formula VIII Product of Formula IB (m.p. in C) Number R5 R8 X Orthoester R2 R5 R8 X 98 H H O trimethyl CH(CH3)2 H H O 58.3; 6.9; 28.3 orthoisobutyrate 58.1; 6.9; 28.5 (154-155) 99 H H S triethyl CH3 H H S 51.0; 5.6; 29.8 orthoacetate 50.9; 5.5; 30.1 (145-148) 100 H H S triethyl CH2CH3 H H S 53.0; 6.1; 28.1 orthopropionate 52.7; 6.0; 28.3 (125-126) 101 H H S trimethyl CH2CH2CH3 H H S 54.7; 6.5; 26.6 orthobutyrate 54.6; 6.4; 26.7 (137-138) Table IV Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Example of Formula VIII Product of Formula IB (m.p. in C) Number R5 R8 X Orthoester R2 R5 R8 X 102 H H O trimethyl H H H O 52.7; 5.4; 34.1 orthoformate 52.2; 5.3; 34.2 (202-204) 103 H H O triethyl CH2CH3 H H O 56.6; 6.5; 30.0 orthopropionate 56.5; 6.3; 30.2 (164-165) EXAMPLE 104 Preparation of 2,5-Di( isopropyl)-7-(4- thiomorpholino)-l,2,4-triazolo[l,5-c]pyrimidine A mixture of 4.00 g (15.8 mmole) of 4-hydrazino 2-isopropyl-6-(4-thiomorpholino)pyrimidine, 2.40 g (16.2 mmole) of trimethyl isobutyrate, 0.95 g (15.8 mmole) of acetic acid and 40 ml of dimethyl sulfoxide was heated at 1200C for about 65 hours and then poured into 200 ml of ice water. The mixture was basified with 10 percent aqueous sodium hydroxide and extracted four times with 50 ml of chloroform. The extracts were washed six times with 150 ml of water, dried over magnesium sulfate and evaporated to provide a dark oil. Nuclear magnetic resonance spectral analysis indicated that the oil was chiefly the desired product. The product was chromatographed on 70 g of silica gel, eluting sequentially with 600 ml of dichloromethane, one liter of 50:50 ethyl acetate:dichloromethane, and ethyl acetate, 100 ml fractions being taken. Fractions 7, 8 and 9 provided 3.35 g (70%} of brown oil. The oil was dissolved in 50 ml of ethanol, and sulfuric acid (1.09 g, 10.7 mmole) and 200 ml of diethyl ether were then added sequentially. The precipitate was collected by filtration, washed with diethyl ether and dried. The product was off-white solid 2,5-di(isopropyl)-7-(4-thiomorpholino) 1,2,4-triazololl,5-cIpyrimidine dihydrogen sulfate, m.p. 192-194 C. Analysis: Calculated for C15H23N5S H2S04 %Cr 44.6; %H, 6.3; %N, 17.4; Found: %C, 44.6; %H, 6.3; %N, 17.5. The structure was confirmed by infrared and nuclear magnetic resonance spectral analyses. Examples 105-127 Using the method of Example 104, the indicated intermediates of Formula VIII were reacted with the indicated orthoesters to provide the indicated compounds of Formula IB (Table V). Table V Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Example of Formula VIII Product of Formula IB (m.p. in C) Number R5 R8 X Orthoester R2 R5 R8 X 105 CH2CH3 H S trimethyl CH(CH3)2 CH2CH3 H S (as H2SO4 Salt): orthoisovalerate 44.6; 6.2; 17.4 44.5; 6.5; 17.6 (155-156) 106 CH(CH3) H S triethyl CH2CH(CH3)2 CH(CH3)2 H S (as H2SO4 Salt): orthoisovalerate 46.0; 6.5; 16.8 45.9; 6.7; 16.9 (169-170) 107 CH2CH3 H S triethyl (CH2)3CH3 CH2CH3 H S (as H2SO4 Salt): orthovalerate 44.6; 6.2; 17.4 44.3; 6.2; 17.7 (132-135) 101 H H S trimethyl CH2CH2CH3 H H S 54.7; 6.5; 26.6 orthobutyrate 54.6; 6.4; 26.7 (137-138) Table V Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Example of Formula VIII Product of Formula IB (m.p. in C) Number R5 R8 X Orthoester R2 R5 R8 X 108 (CH2)2CH3 H S trimethyl (CH2)3CH3 (CH2)2CH3 H S (as H2SO4 Salt): orthovalerate 46.0; 6.5; 16.8 46.0; 6.4; 17.1 (152-153) 109 CH2CH(CH3)2 H S trimethyl CH(CH3)2 CH2CH(CH3)2 H S 60.1; 7.9; 21.9 orthoisobutyrate 59.7; 7.9; 21.7 (94-97) 110 CH2CH(CH3)2 H O triethyl CH2CH3 CH2CH(CH3)2 H O 62.2; 8.0; 24.2 orthopropionate 62.0; 7.7; 24.2 (119-122) 101 CH2CH(CH3)2 H O trimethyl CH(CH3)2 CH2CH(CH3)2 H O 63.3; 8.3; 23.1 orthoisobutyrate 63.2; 8.0; 23.1 (93-95) Table V Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Example of Formula VIII Product of Formula IB (m.p. in C) Number R5 R8 X Orthoester R2 R5 R8 X 112 CH2CH(CH3)2 H O trimethyl (CH2)3CH3 CH2CH(CH3)2 H O 64.3; 8.6; 22.1 orthovalerate 63.7; 8.2; 21.9 (85-88) 113 (CH2)3CH3 H S trimethyl CH3 (CH2)3CH3 H S 57.7; 7.7; 24.0 orthoacetate 57.3; 7.3; 24.1 (123-126) 114 (CH2)3CH3 H S trimethyl (CH2)2CH3 (CH2)3CH3 H S 60.3; 7.9; 22.0 orthobutyrate 59.9; 8.0; 21.9 (66-68) 115 (CH2)3CH3 H S trimethyl CH2CH(CH3)2 (CH2)3CH3 H S 61.4; 8.2; 21.1 orthoisovalerate 60.9; 8.3; 21.1 (50-53) Table V Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Example of Formula VIII Product of Formula IB (m.p. in C) Number R5 R8 X Orthoester R2 R5 R8 X 116 CH2CH(CH3)2 H O triethyl H CH2CH(CH3)2 H O 59.7; 7.3; 26.8 orthoformate 59.6; 7.2; 26.9 (123-126) 117 (CH2)3CH3 H S triethyl CH2CH3 (CH2)3CH3 H S 59.0; 7.6; 22.9 orthopropionate 59.2; 7.7; 23.3 (110-112) 118 (CH2)3CH3 H O trimethyl (CH2)3CH3 CH2CH3 H O 62.3; 8.0; 24.2 orthovalerate 62.1; 8.0; 24.3 (87-89) 119 (CH2)3CH3 H O trimethyl (CH2)3CH3 (CH2)2CH3 H O 63.3; 8.3; 23.1 orthovalerate 63.1; 8.2; 23.3 (105-106 Table V Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Example of Formula VIII Product of Formula IB (m.p. in C) Number R5 R8 X Orthoester R2 R5 R8 X 120 (CH2)3CH3 H O trimethyl CH3 (CH2)3CH3 H O 61.1; 7.7; 25.4 orthoacetate 61.0; 7.8; 25.3 (132-133) 121 (CH2)3CH3 H O trimethyl CH2CH3 (CH2)3CH3 H O 62.3; 8.0; 24.2 orthopropionate 62.1; 8.1; 24.2 (105-106) 122 (CH2)3CH3 H O trimethyl (CH2)2CH3 (CH2)3CH3 H O 63.3; 8.3; 23.1 orthobutyrate 63.3; 8.4; 23.2 (98-99) 123 (CH2)3CH3 H O trimethyl CH2CH(CH3)2 (CH2)3CH3 H O 64.3; 8.6; 22.1 orthoisovalerate 64.2; 8.4; 22.0 (73-75) Table V Calculated: %C; %H; %N Intermediate Found: %C, %H, %N Example of Formula VIII Product of Formula IB (m.p. in C) Number R5 R8 X Orthoester R2 R5 R8 X 124 CH2CH(CH3)2 H S trimethyl CH2CH3 CH2CH(CH3)2 H S 59.0; 7.6; 22.9 orthopropionate 59.0; 7.2; 23.1 (124-126) 125 (CH2)2CH3 H O trimethyl CH2CH(CH3)2 (CH2)3CH3 H O 63.3; 8.3; 23.1 orthoisovalerate 63.1; 7.9; 23.2 (53-55) 126 CH2CH(CH3)2 H S trimethyl H CH2CH(CH3)2 H S 56.3; 6.9; 25.2 orthoformate 56.3; 6.9; 25.4 (134-136) 127 CH2CH3 H O trimethyl CH2CH(CH3)2 CH2CH3 H O 62.3; 8.0; 24.2 orthoisovalerate 62.3; 7.9; 24.3 (50-52) EXAMPLE 128 Part A Preparation of 4-Chloro-2-methyl-6-(4 morpholino)pyrimidine by Scheme I, Step (5) A solution of 5.00g g (31.7 mmole) of 4,6-dichloro-2-methylpyrirnidine and 6.00 g (68.9 mmole) of morpholine in 50 ml of water was heated on a steam cone for about 18 hours. The mixture was diluted with water and cooled. The resulting white solid was separated by filtration, washed with water and dried to provide 4.84 g (72%) of 4-chloro-2-methyl-6-(4-morpholino)pyrimidine. The structural assignment was confirmed by infrared and nuclear magnetic resonance spectral analyses. Part B Prepartion of 4-Hydrazino-2-methyl-6-(4- morpholino)p.yrimidine by Scheme I, Step (6) To a mixture of 4.70 g (22 mmole) of 4-chloro-2-methyl-6-(4-morpholino)pyrimidine in 50 ml of ethanol was added 2.2 g (44 mmole) of hydrazine hydrate and the mixture was heated at its reflux temperature for 16 hours. Cooling provided a precipitate which was separated by filtration and washed with ethanol to provide 3.15 g (68%) of white solid 4-hydrazino-2-methyl-6-(4morpholino)pyrimidine. The structural assignment of the product was confirmed by infrared and nuclear magnetic resonance spectral analyses and comparison with the same compound made in Example 9. Examples 129-131 Using the method of Example 128, Part A, the indicated intermediate of Formula V was reacted with the indicated amine of Formula VIA to provide the indicated intermediate of Formula VII. The intermediate of Formula VII was then reacted with hydrazine hydrate in accordance with the method of Example 128, Part B, to provide the indicated intermediate of Formula VIII (Table VI). Table VI EMI56.1 Example <SEP> Intermediate <SEP> Heterocyclic <SEP> Intermediate <SEP> Intermediate <tb> Number <SEP> of <SEP> Formula <SEP> V <SEP> Amine <SEP> of <SEP> Formula <SEP> VII <SEP> of <SEP> Formula <SEP> VII <tb> <SEP> 129 <SEP> # <SEP> # <SEP> # <SEP> # <tb> <SEP> m.p. <SEP> 147.5-150 C, <SEP> White <SEP> Solid <SEP> White <SEP> Solid <tb> <SEP> 130 <SEP> # <SEP> # <SEP> # <SEP> # <tb> <SEP> m.p. <SEP> 210-220 C, <SEP> White <SEP> Solid <SEP> m.p. <SEP> 232-234 C, <SEP> White <SEP> Solid <tb> Table Vi (continued) EMI57.1 Example <SEP> Intermediate <SEP> Heterocyclic <SEP> Intermediate <SEP> Intermediate <tb> Number <SEP> of <SEP> Formula <SEP> V <SEP> Amine <SEP> of <SEP> Formula <SEP> VII <SEP> of <SEP> Formula <SEP> VII <tb> <SEP> 131 <SEP> # <SEP> # <SEP> # <SEP> # <tb> <SEP> m.p. <SEP> about <SEP> 200 C <SEP> m.p. <SEP> 250-253 C, <SEP> White <SEP> Solid <tb> EXAMPLE 132 Preparation According to Scheme II 5-Methylthio-7- C 4-morphol ino ) -1,2, 4-triazolo- [4,3-clpyrimidine and 5,7-Bis(4-morpholino) 1,2,4-triazolo[1,5-C]pyrimidine Part A Preparation of 4-Hydrazinyl-2-methylthio-6 (4-morpholino)pyrimidine according to Scheme II, Step (1) To a solution of 3.0 g (15.7 mmole) of 4-chloro-6-hydrazinyl-2-methylthiopyrimidine in 50 ml of water was added 2.8 g (32.2 mole) of morpholine, and the mixture was heated at reflux for two days. Cooling gave a precipitate which was separated by filtration, washed with water and dried to provide off-white solid 4-hydrazinyl2-methylthio-6-(4-morpholino)pyrimidine, m.p. 134-1440C. The structural assignment was confirmed by infrared and nuclear magnetic resonance spectral analyses. Part B Preparation of 5-Methylthio-7-(4 morpholino)-1,2,4-triazolo[4,3-clpyrimidine according to Scheme II, Step (2) A mixture of 24.75 g (103 mmole) of 4-hydrazinyl-2-methylthio-6-( 4-morpholino)pyrimidine and 200 ml of triethyl orthoformate was heated at 1200C in an open flask for 60 hours. The mixture was cooled, then diluted with 300 ml of diethyl ether. The precipitate was separated by filtration, washed with ether and dried to provide 5-methylthio-7- ( 4-morphol ino) -1,2, 4-triazolo t4,3-clpyrimidine, m.p. 212-2130C after two recrystallizations from chloroform-hexane. Part C Preparation of 5,7-Bis(4-morpholino)-l,2,4- triazolo[l,5-c]pyrimidine according to Scheme II, Step (3) A mixture of 7.10 g (28.3 mmole) of Smethylthio-7-(4-morpholino)-lr2,4-triazolotlr5-cl- pyrimidine and 35 ml of morpholine was heated at reflux for 16 hours. Cooling of the mixture provided a solid. The mixture was dil-uted to a total volume of 100 ml with diethyl ethe'r, cooled and the product separated by filtration. Recrystallization with treatment with decolorizing charcoal from a mixture of benzene and hexane (1:1) provided white solid 5,7-bis(4-morpholino)-1,2,4triazolo[l,5-c]pyrimidine, m.p. 176-1770C. Analysis: Calculated for C13H18N662: %C, 53.8; tH, 6.2; %N, 29.0; Found: %C, 53.8; %H, 6.1: %N, 28.9. The structural assignment was confirmed by infrared and nuclear magnetic resonance spectral analyses. Examples 133-135 Using the method of Example 132, Part A, the indicated intermediates of Formula XI were prepared from 4-chloro-6-hydrazino-2-methylthiopyrimidine and the indicated amine of Formula VIA (Table VII). The structures of the intermediates of Formula XI were confirmed by infrared and nuclear magnetic resonance spectral analyses. Table VII EMI60.1 <tb> <SEP> Amine <SEP> Reactant <SEP> Intermediate <tb> Example <SEP> of <SEP> Formula <SEP> VIA <SEP> of <SEP> Formula <SEP> XI <tb> <SEP> CH3 <tb> 133 <SEP> HtyNCH3 <SEP> N <tb> 133 <SEP> CH3 <SEP> NHNH2 <tb> <SEP> CH3N <tb> <SEP> \ <SEP> pCH3 <tb> <SEP> HN <SEP> N·CHN3 <tb> 134 <SEP> / <SEP> I <SEP> 11 <tb> <SEP> NHNHZ <tb> <SEP> 7 <SEP> BCHs <tb> <SEP> HN <SEP> S <SEP> NSHN <tb> 135 <SEP> \ <SEP> l <SEP> ll <tb> <SEP> e <SEP> N <SEP> vNHNH <SEP> 2 <tb> <SEP> 5(·N <SEP> 2 <tb> Examples 136-138 Using the method of Example 132, Part B, the indicated compounds of Formula IA were prepared from the indicated intermediate of Formula XI (Table VIII). The structures of the compounds of Formula IA were confirmed by infrared and nuclear magnetic resonance spectral analyses. Table VIII EMI61.1 <tb> <SEP> Intermediate <SEP> of <SEP> Compound <SEP> of <tb> Example <SEP> Formula <SEP> XI <SEP> Formula <SEP> IA <tb> <SEP> 136 <SEP> Example <SEP> 133 <SEP> SCH3 <tb> <SEP> 4 <SEP> N+N <tb> <SEP> C <SEP> N/4N <tb> <SEP> H3C-NX <tb> <SEP> 137 <SEP> Example <SEP> 134 <SEP> CH3 <tb> <SEP> Ne <SEP> N <SEP> AN <tb> <SEP> 31 <SEP> 8 <tb> <SEP> H <SEP> N <tb> <SEP> 138 <SEP> Example <SEP> 135 <SEP> çCH3 <tb> <SEP> No <SEP> NwN <tb> Examples 139-141 Using the method of Example 132, Part C, the indicated compounds of Formula IB were prepared from the indicated compound of Formula IA and the indicated amine of Formula VIA (Table IX). Chromatographic separations were used to obtain the desired [1,5-c] isomers. Table IX EMI63.1 <SEP> Compound <SEP> Amine <SEP> of <SEP> Calculated: <SEP> %C; <SEP> %H; <SEP> %N <tb> Example <SEP> of <SEP> Formula <SEP> IA <SEP> Formula <SEP> VIA <SEP> Product <SEP> of <SEP> Formual <SEP> IB <SEP> Found: <SEP> %C; <SEP> %H, <SEP> %N <tb> <SEP> 139 <SEP> Example <SEP> 136 <SEP> # <SEP> # <SEP> 55.4; <SEP> 7.0; <SEP> 32.3 <tb> <SEP> 55.9; <SEP> 6.9; <SEP> 31.8 <tb> <SEP> (m.p. <SEP> 142-143.5 C) <tb> <SEP> 140 <SEP> Example <SEP> 137 <SEP> # <SEP> # <SEP> 51.1; <SEP> 6.3; <SEP> 32.1 <tb> <SEP> 51.5; <SEP> 6.3; <SEP> 31.8 <tb> <SEP> (m.p. <SEP> 127-130 C) <tb> <SEP> 141 <SEP> Example <SEP> 138 <SEP> # <SEP> # <SEP> 51.0; <SEP> 5.9; <SEP> 27.4 <tb> <SEP> 50.7; <SEP> 5.9; <SEP> 27.6 <tb> <SEP> (m.p. <SEP> 169-170 C) <tb> EXAMPLE 142 The Preparation of 2,7-Dimethyl-5-(1 piperazino)-1,2,4-triazolo[I,5-c]pyrimidine according to Scheme III A solution of the known compound 5-chloro-2,7-dimethyl-1,2,4-triazolo[1,5-clpyrimidine (2.0 g, 11 mmole) in 50 ml of dioxane was added dropwise to a suspension of 120 g (140 mmole) of piperazine in 75 ml of dioxane. After stirring for 3 hours at 200C, the mixture was diluted with 150 ml of water and then extracted with three 150 ml portions of chloroform. The extracts were washed with two 150 ml portions of water and two 100 ml portions of saturated sodium chloride solution and were then dried over magnesium sulfate. The extracts were evaporated to provide a residue which was recrystallized with treatment with decolorizing charcoal from a benzenehexane mixture (1:3) to provide white solid 2,7-dimethyl-5 (l-piperazino)-1,2r4-triazolotl,5-c]pyrimidine, m.p. 108-1100C. Analysis: Calculated for CllH16N6: %C, 56.9; %H, 6.9; %N, 36.2; Found: %C, 57.0; %H, 6.9; %N, 35.6. Examples 143-156 Using the method of Example 142, the indicated compounds of Formula IB were prepared from the indicated intermediates of Formula XIV and the indicated amines of Formula VIA (Table X). Table X EMI65.1 <SEP> Intermediate <tb> <SEP> of <SEP> Formula <SEP> XIV <SEP> Product <SEP> of <SEP> Formula <SEP> IB <SEP> Calculated: <SEP> %C, <SEP> %H, <SEP> %N <tb> <SEP> Amine <SEP> of <SEP> Found: <SEP> %C; <SEP> %H; <SEP> %N <tb> Example <SEP> R2 <SEP> R7 <SEP> R8 <SEP> Formula <SEP> VIA <SEP> R2 <SEP> R5 <SEP> R7 <SEP> R8 <SEP> (m.p. <SEP> in <SEP> C) <tb> <SEP> 143 <SEP> CH3 <SEP> CH3 <SEP> H <SEP> # <SEP> CH3 <SEP> # <SEP> CH3 <SEP> H <SEP> 58.5; <SEP> 7.4; <SEP> 34.1 <tb> <SEP> 58.8; <SEP> 7.3; <SEP> 34.8 <tb> <SEP> (106.5-107.5) <tb> <SEP> 144 <SEP> CH3 <SEP> CH3 <SEP> H <SEP> # <SEP> CH3 <SEP> # <SEP> CH3 <SEP> H <SEP> 47.0; <SEP> 5.4; <SEP> 24.9 <tb> <SEP> 47.0; <SEP> 5.3; <SEP> 25.4 <tb> <SEP> (201-203) <tb> <SEP> 145 <SEP> CH3 <SEP> CH3 <SEP> H <SEP> # <SEP> CH3 <SEP> # <SEP> CH3 <SEP> H <SEP> 49.8; <SEP> 5.7; <SEP> 26.4 <tb> <SEP> 50.0; <SEP> 5.6; <SEP> 26.8 <tb> <SEP> (186-188) <tb> <SEP> 146 <SEP> CH3 <SEP> CH3 <SEP> H <SEP> # <SEP> CH3 <SEP> # <SEP> CH3 <SEP> H <SEP> 53.0; <SEP> 6.1; <SEP> 28.1 <tb> <SEP> 53.0; <SEP> 6.1; <SEP> 28.7 <tb> <SEP> (133-134) <tb> Table X (continued) EMI66.1 <SEP> Intermediate <tb> <SEP> of <SEP> Formula <SEP> XIV <SEP> Product <SEP> of <SEP> Formula <SEP> IB <SEP> Calculated: <SEP> %C, <SEP> %H, <SEP> %N <tb> <SEP> Amine <SEP> of <SEP> Found: <SEP> %C; <SEP> %H; <SEP> %N <tb> Example <SEP> R2 <SEP> R7 <SEP> Formula <SEP> VIA <SEP> R2 <SEP> R5 <SEP> R7 <SEP> R8 <SEP> (m.p. <SEP> in <SEP> C) <tb> <SEP> 147 <SEP> CH3 <SEP> CH3 <SEP> # <SEP> CH3 <SEP> # <SEP> CH3 <SEP> H <SEP> 56.6; <SEP> 6.5; <SEP> 30.0 <tb> <SEP> 56.6; <SEP> 6.4; <SEP> 30.5 <tb> <SEP> (142-144) <tb> <SEP> 148 <SEP> H <SEP> CH3 <SEP> # <SEP> H <SEP> # <SEP> CH3 <SEP> H <SEP> 51.0; <SEP> 5.6; <SEP> 29.8 <tb> <SEP> 50.7; <SEP> 6.6; <SEP> 29.8 <tb> <SEP> (99.5-100) <tb> <SEP> 149 <SEP> H <SEP> CH3 <SEP> # <SEP> H <SEP> # <SEP> CH3 <SEP> H <SEP> 48.7; <SEP> 5.2; <SEP> 27.9 <tb> <SEP> 48.1; <SEP> 5.2; <SEP> 28.3 <tb> <SEP> (188-190) <tb> <SEP> 150 <SEP> H <SEP> CH3 <SEP> # <SEP> H <SEP> # <SEP> CH3 <SEP> H <SEP> 44.9; <SEP> 4.9; <SEP> 26.2 <tb> <SEP> 44.7; <SEP> 5.0; <SEP> 26.3 <tb> <SEP> (222-223) <tb> Table X (continued) EMI67.1 <SEP> Intermediate <tb> <SEP> of <SEP> Formula <SEP> XIV <SEP> Product <SEP> of <SEP> Formula <SEP> IB <SEP> Calculated: <SEP> %C, <SEP> %H, <SEP> %N <tb> <SEP> Amine <SEP> of <SEP> Found: <SEP> %C; <SEP> %H; <SEP> %N <tb> Example <SEP> R2 <SEP> R7 <SEP> Formula <SEP> VIA <SEP> R2 <SEP> R5 <SEP> R7 <SEP> R8 <SEP> (m.p. <SEP> in <SEP> C) <tb> <SEP> 151 <SEP> CH2CH3 <SEP> CH3 <SEP> # <SEP> CH2CH3 <SEP> # <SEP> CH3 <SEP> H <SEP> 54.7; <SEP> 6.5; <SEP> 26.7 <tb> <SEP> 54.7; <SEP> 6.7; <SEP> 27.2 <tb> <SEP> (106-107) <tb> <SEP> 152 <SEP> CH2CH3 <SEP> CH3 <SEP> # <SEP> CH2CH3 <SEP> # <SEP> CH3 <SEP> H <SEP> 51.6; <SEP> 6.1; <SEP> 25.1 <tb> <SEP> 51.5; <SEP> 6.3; <SEP> 25.0 <tb> <SEP> (146-148) <tb> <SEP> 153 <SEP> CH2CH3 <SEP> CH3 <SEP> # <SEP> CH2CH3 <SEP> # <SEP> CH3 <SEP> H <SEP> 48.8; <SEP> 5.8; <SEP> 23.7 <tb> <SEP> 48.8; <SEP> 6.0; <SEP> 24.3 <tb> <SEP> (183-186) <tb> <SEP> 154 <SEP> CH3 <SEP> H <SEP> # <SEP> CH3 <SEP> # <SEP> H <SEP> H <SEP> 51.0; <SEP> 5.6; <SEP> 29.8 <tb> <SEP> 51.0; <SEP> 5.5; <SEP> 30.0 <tb> <SEP> (83-85) <tb> Table X EMI68.1 <SEP> Intermediate <tb> <SEP> of <SEP> Formula <SEP> XIV <SEP> Product <SEP> of <SEP> Formula <SEP> IB <SEP> Calculated: <SEP> %C, <SEP> %H, <SEP> %N <tb> <SEP> Amine <SEP> of <SEP> Found: <SEP> %C; <SEP> %H; <SEP> %N <tb> Example <SEP> R2 <SEP> R7 <SEP> Formula <SEP> VIA <SEP> R2 <SEP> R5 <SEP> R7 <SEP> R8 <SEP> (m.p. <SEP> in <SEP> C) <tb> <SEP> 155 <SEP> CH3 <SEP> H <SEP> # <SEP> CH3 <SEP> # <SEP> H <SEP> H <SEP> 47.8; <SEP> 5.2; <SEP> 27.9 <tb> <SEP> 48.0; <SEP> 5.3; <SEP> 28.0 <tb> <SEP> (150-153) <tb> <SEP> 156 <SEP> CH3 <SEP> H <SEP> # <SEP> CH3 <SEP> # <SEP> H <SEP> H <SEP> 44.9; <SEP> 4.9; <SEP> 26.2 <tb> <SEP> 45.0; <SEP> 4.9; <SEP> 25.9 <tb> <SEP> (183-185) <tb> EXAMPLE 157 Preparation of 7-Methyl-5-(l-piperazinyl) 1,2,4-triazolo[4,3-c]pyrimidine and 7-Methyl-5 (l-piperazinyl)-1,2,4-triazolo[1,5-c]pyrimidine by Scheme IV A mixture of 6.00 g (33.3 mmole) of 7-methyl-5-methylthio-1,2,4-triazolo[4,3-c]pyrimidine, 30.0 g (0.35 mmole) of piperazine and 250 ml of dioxane was refluxed under nitrogen for six days. The mixture was cooled and concentrated in vacuo. The residue obtained was dissolved in 150 ml of water, and the solution was extracted four times with 150 ml portions of chloroform. The extracts were washed thrice with 150 ml portions of water and twice with 150 ml portions of sodium chloride solution and were dried over magnesium sulfate. Evaporation provided a yellow solid which was taken up in 150 ml of chloroform, filtered and chromatographed on a high pressure liquid chromatograph, eluting with methanol-ethyl acetate (1:1). Infrared and nuclear magnetic resonance spectral analyses showed fractions 2 and 3 to be 7-methyl-5-(l-piperazino)-1,2,4-triazolo[1,5-c]- pyrimidine, m.p. 92-95 C. Analysis: Calculated for C10H14N6: %C, 55.0; %H, 6.5; %N, 38.5; Found: %C, 54.8; %H, 6.4; %N, 38.3. Fraction 4 contained about 15% of 7-methyl-5-(l-piperazino)-1,2,4-triazolo[4,3-c]pyrimidine, m.p. 136-1390C. Analysis: Calculated for C10H14N6: %C, 55.0; %H, 6.5; %N, 38.5. Found: %C, 54.5; %H, 6.4; %N, 37.9. EXAMPLE 158 Preparation of 7-Methyl-5-(4-piperazinyl)- 1,2,4-triazolo[4,3-c]pyrimidine and 7-Methyl-5- ( 4-methyl-1-piperazinyl )- 1,2,4-triazolo[1,5-c]pyrimidine Using the method of Example 157, 7-methyl-5 methylthio-l,2,4-triazolo[4,3-c]pyrimidine was reacted with N-methylpiperazine to provide a mixture of 7-methyl-5 (4-methyl-1-piperazinyl)-1,2,4-triazolo[4,3-c]pyrimidine, m.p. 170-1710C (Analysis: Calculated for C11H14N6: %C, 56.9; %H, 6.9; %N, 36.2; Found: EC, 57.0; %H, 6.9; %N, 35.9) and 7-methyl-5-(4-methyl-1-piperazinyl)-1,2,4triazolo[1,5-c]pyrimidine, m.p. 95-980C. These compounds were separated by high pressure liquid chromatography using 5% methanol in ethyl acetate which contained a small amount of diethylamine. EXAMPLE 159 Preparation of 7-Methyl-S- (4-morpholino)- 1,2,4-triazolo[4,3-c]pyrimidine and 7-Methyl 5-(4-morpholino)-1,2,4-triazolo[1,5-c]pyrimidine A mixture of 6.0 g (33 mmole) of 7-methyl-5 methylthio-1,2,4-triazolo[4,3-c3pyrimidine and 15 ml of morpholine was heated at reflux for 19 hours, cooled and diluted with diethyl ether and hexane. The solid product was separated by filtration and chromatographed on florisil, eluting sequentially with benzene, 10% ethyl acetate in benzene, 50% ethyl acetate in benzene, and ethyl acetate. Early fractions were recrystallized from a benzene-hexane mixture to provide 7-methyl-5-(4morpholino)-1,2,4-triazolo[1,5-c]pyrimidine, m.p. 113-1140C. Later fractions were recrystallized from an ethyl acetate-hexane mixture with treatment with decolorizing charcoal to provide 7-methyl-5-(4- morpholino)-1,2,4-triazolo[4,3-c]pyrimidne, m.p. 209-100C. Analysis: Calculated for C10H13N50: %C, 54.8; %H, 6.0; %N, 31.9; Found: %C, 55.1; %H, 5.9; %N, 31.8. EXAMPLE 160 To a solution of 3.00 g (10.8 mmole) of 2,5diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c]pyrimidine in 60 ml of warm ethanol was added 1.05 g (10.7 mmole) of concentrated sulfuric acid. The solution was diluted to 250 ml with diethyl ether and let stand for two hours. The precipitated product was separated by filtration and washed with ether and dried to provide 2,5-diethyl-7-(4-thiomorpholino)-l,2,4-triazolo[l,5-c] pyrimidine dihydrogen sulfate as a white solid, m.p. 178-1800C. Analysis: Calculated for C13Hl9H5SH2So4: %C, 41.5; %H, 5.6; %N, 18.7; Found: %C, 41.7; %H, 5.7; %N, 19.0. Example 161 To a solution of 1.75 g (6.31 mmole) of 2,5-diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c]pyrimidine in 20 ml of dioxane was added 1.0 ml of 6.4 M hydrogen chloride (6.4 mmole) in ethanol. The solution was diluted with 100 ml of diethyl ether and allowed to stand several hours. The white solid was separated by filtration and dried to provide 2,5-diethyl-7-(4-thiomorpholino) 1,2,4-triazolo[l,5-c]pyrimidine hydrochloride hydrate, m.p. 113-1140C. Analysis: Calculated for C13H19N5S.HCl.H2O: %C, 47.0; ZH, 6.7; %N, 21.1; Found: %C, 46.9; %H, 6.8; ZN, 21.3. Example 162 To a solution of 2.00 g (7.21 mmole) of 2,5-diethyl-7-(4-thiomorpholion)-1,2,4-triazolo[1,5-c]pyrimidine in 20 ml of warm ethanol was added 0.85 g (7.4 mmole) of phosphoric acid. The solution was diluted with 75 ml of diethyl ether and allowed to stand. After a few minutes the white solid was separated by filtration, washed with diethyl ether and dried to provide 2,5-diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c]pyrimidine trihydrogen phosphate hydrate, m.p. 154-155"C. Analysis: Calculated for Cl3Hl9N5s H3P04 H20: %C, 36.4; %H, 6.6; EN, 16.3; Found: %C, 36.5; %H, 5.8; ZN, 16.6. Examples 163-164 Using the method of Example 1, Part E, the indicated amines of Formula VIA were reacted with the indicated known 4-chloro-2-alkyl-6-hydrazinylpyrimidines of Formula VI to provide the novel intermediates of Formula VIII (Table XI). Table XI EMI72.1 <SEP> Pyrimidine <tb> <SEP> Amine <SEP> Intermediate <SEP> Melting <SEP> Point <tb> Example <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VI <SEP> Intermediate <SEP> of <SEP> Formula <SEP> VIII <SEP> (in <SEP> C) <tb> <SEP> 163 <SEP> # <SEP> # <SEP> # <SEP> none <SEP> taken <tb> <SEP> 164 <SEP> # <SEP> # <SEP> # <SEP> 140-143 <tb> Examples 165-171 Using the method of Part F, Example 1, the indicated intermediates of Formula VIII were reacted with the indicated trialkyl orthoesters to provide the indicated compounds of Formula IA (Table XII). Table XII Calculated: %C; %H; %N Intermediate Found: %C; %H; %N Ex. of Formula VIII Ortho Ester Product of Formula IA (m.p. in C) R5 R8 X R8 R5 R8 X 165 C6H5 H O triethyl H C6H5 H O 64.0; 5.4; 24.9 orthoformate 63.8; 5.2; 24.7 ( > 280) 166 H H S trimethyl H H H S 48.8; 5.0; 31.7 orthoformate 48.2; 4.9; 31.3 (177-179 167 H H NCH3 trimethyl H H H NCH3 55.0; 6.5; 38.5 orthoformate 54.9; 6.4; 38.1 (167-170) Table XII (Continued) Calculated: %C; %H; %N Ex. Intermediate Found: %C; %H; %N No. of Formula VIII Ortho Ester Product of Formula IA (m.p. in C) R5 R8 X R3 R5 R8 X 168 CH3 H NCH3 triethyl H CH3 H NCH3 56.9; 6.9; 36.2 orthoformate 56.8; 6.8; 36.3 (177-179) 169 (CH2)2CH3 H NCH3 triethyl CH2CH3 (CH2)2CH3 H NCH3 62.5; 8.4; 29.1 orthopropionate 61.9; 8.5; 29.3 (126-129) 170 H H S triethyl CH2CH3 H H S 53.0; 6.1; 28.1 orthopropionate 53.1; 6.2; 28.1 (125-127) 171 (CH2)2CH3 H NCH3 triethyl H (CH2)2CH3 H NCH3 60.0; 7.7; 32.2 orthoformate 59.5; 7.7; 32.0 (162-163) EXAMPLE 172 Preparation of 3-Methyl-5-methylthio-8 phenyl-7- ( 4-thiomorpholino) -1,2, 4-triazolo- [4,3-c]pyrimidine according to Scheme IV Hart Preparation of 4-Chloro-2-methylthio-5 phenyl-6- ( 4-thiomorpholino) pyrimidine A mixture of 25 g (0.093 mole) of 4,6-dichloro-2-methylthio-5-phenylpyrimidine and 20 g (0.19 mole) of thiomqrpholine in 100 ml of methanol was stirred for 16 hours. The solid was separated by filtration and ied to provide white crystals of crude 4-chloro-2-methyl thio-S-phenyl-6-(4-thiomorpholino)pyrimidine, m.p. 110-125 C. Part B Preparation of 4-Hydrazino-2-methylthio- 5-phenyl-6-(4-thiomorpholino)pyrimidine A mixture of 29 g (0.086 mole) of 4-chloro-2-methylthio-S-phenyl-6- (4-thiomorphol ino) pyrimidine and 10.0 g (0.2 mole) of hydrazine hydrate in 200 ml of ethanol was heated at its reflux temperature for 70 hours. The mixture was cooled and the product was separated by filtration. The product was white crystals of 4-hydrazino-2-methylthio-5-phenyl-6-(4-thiomorpholino) pyrimidine, m.p. 170-171 C. The structure was confirmed by infrared and nuclear magnetic resonance spectral analyses. Part C Preparation of 3-Methyl-5-methylthio-8-phenyl 7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c]pyrimidine A mixture of 4.2 g (0,012 mole) of 4-hydrazino-2-methylthio-5-phenyl-6- ( 4-thiomorpholino) - pyrimidine and 40 ml of triethyl orthoacetate was heated at its reflux temperature for about 64 hours, and was then allowed to cool. The solid precipitate was collected by filtration, washed with hexane and dried. Recrystallization from ethyl acetate provided 3.0 g of pale green crystals of 3-methyl-5-methylthio-8-phenyl-7-(4-thiomorpholino)-1,2,4-triazolo(4,3-c)pyrimidine, m.p. 171-172 C. This solid was dissolved in 40 ml of hot ethanol and an equimolar amount of sulfuric acid was added. The mixture was cooled aid diethyl ether was added to precipitate yellow crystals of 3-methyl-5-methylthio-8phenyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c]pyrimidine dihydrogen sulfate, m.p. 193-195 C. The salt was neutralized with ammoniu hydroxide to reprecipitate the free base which was again recrystallized from ethyl acetate. Analysis: Calculated for C17H19N5S2: %C, 57.1; %H, 5.4; %N, 19.6; Found: %C, 56.5; %H, 5.4; %N,19.7. EXAMPLE 173 Preparation of 3-ethyl-5-methylthio-8-phenyl 7-(4-thiomorpholino)-1,2,4-triazolo[4,3- pyrimidine. Using the method of Example 172, part C, the intermediate of Example 172, part B, was reacted with triethyl orthopropionate to provide 3-ethyl-5-methylthio-8 phenyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c]pyrimidine dihydrogen sulfate, m.p. 205-207 c. Analysis: Calculated for C18H21N5S2-H2S 4: %C,46.0; %H, 4.9; %N, 14.9; Found: %C, 45.9; %H, 5.1; %N, 14.9. The crude free base had a melting point of 152-1550C. EXAMPLE 174 Preparation of 2,S-Diethyl-7-[4-(1-dioxothio- morpholino] -1,2 ,4-triazolo[l ,5-c] pyrimidine To a stirred solution of 5.5g (20 mmoles) of 2,5-diethyl-7-[4-(thiomorpholino]-1,2,4-triazolo- [1,5-c]pyrimidine in 100 ml of chloroform was added dropwise 8.6 g (50 mmoles) of meta-chloroperbenzoic acid in 100 ml of chloroform over 3.5 hours. The mixture was stirred for an additional 16 hours. Thin layer chromatography showed incomplete reaction. An additional 1.5 g of meta-chloroperbenzoic acid was dissolved in 25 ml of chloroform and the solution was added dropwise over 45 minutes. The mixture was stirred for one additional hour. Thin layer chromatography showed that the reaction had progressed but was still incomplete. An additional 1.5 g of meta-chloroperbenzoic acid was dissolved in 25 ml of chloroform and the solution was added dropwise over 45 minutes. After stirring the mixture for about 90 hours it was washed thrice with 10% aqueous sodium hydroxide solution, once with water and once with saturated sodium chloride solution, and was finally dried over magnesium sulfate. Evaporation provided a white solid which was recrystallized from ethyl acetate. The solid product was separated by filtration and found by thin layer chromatography to be primarily the desired product. A second crop was obtained by adding cyclohexane to the ethyl acetate filtrate. The white solid was collected by filtration and determined by thin layer chromatography to be pure 2,5-diethyl-7-[4-(1-dioxothiomorpholino]-1,2,4triazolo[1,5-c]pyrimidine, m.p . 187-1890C. Analysis: Calculated for C13H19N5O25: ZC, 50.5; %H, 6.2; %N, 22.6; Found: %C, 50.3, GH, 6.1; ZN, 23.0. To a warm solution of l.Og (3.2 mmole) of 2,5-diethyl-7-[4- [1-dioxothiomorpholino]-1,2,4-triazolo[1,5-c]pyrimidine in 50 ml of ethanol was added dropwise 0.30 g (3.1 mmole) of concentrated sulfuric acid. The solution was stirred and allowed to cool to about 20 C, then diluted to a total volume of 300 ml with diethyl ether. After stirring for one hour the solid was collected by filtration, rinsed with ether and dried to provide 2,5-diethyl-7-[4-(1- dioxothiomorpholino]-1,2,4-triazolo[1,5-c]pyrimidine bisulfate, m.p. 189-191 C. Analysis: Calculated for C13H19N5O2S.H2SO4: %C, 38.3; %H, 5.2; %N, 17.2; Found: : %C, 38.5; %H, 5.2; %N, 17.6 EXAMPLE 175 Preparation of 2,5-Diethyl-7-{4-(1-oxothio- morpholino]-1,2,4-triazolo[1,5-c]pyrimidine To a stirred solution of 8.3 g t30 mmoles) of 2,5-diethyl-7-t4-(thiomorpholino3-1,2,4-trìazolo- [1,5-c]pyrimidine in 75 ml of chloroform was added, dropwise over 35 minutes, 80 ml of a chloroform solution of 5.2 g (30 mmoles) of meta-chloroperbenzoic acid. A mild exotherm was observed, and the solution was stirred for an additional 45 minutes. Thin layer chromatography showed incomplete reaction. An additional 0.5 g of meta-chloroperbenzoic acid was dissolved in 10 ml of chloroform and the solution was added dropwise to the reaction mixture. After stirring for an additional 1.5 hours the reaction mixture was washed sequentially with 10% sodium hydroxide solution, water and saturated sodium chloride solution, and was then dried over magnesium sulfate. The dried organic layer was then evaporated to provide an off-white solid residue. Chromatography on silica gel, eluting with 1:9 methanol:chloroform provided starting material in early fractions and product in later fractions. The product was white solid 2,5-diethyl-7 [4-(1-oxothiomorpholino)-l,2,4-triazo1o[l,S-c]pyriidine, m.p. 223-2250C. The structure was confirmed by C13 nuclear magnetic resonance and infrared spectral analyses. Analysis: Calculated for C13H19N50S: %C, 53.2; EH, 6.5; %N, 23.9; found: %C, 53.1; %H, 6.4; %N, 23.8. To a warm solution of 2.5g (8.5 mmoles) of 2,5-diethyl-7-[4-(1-oxothiomorpholino)-1,2,4-triazolo [1,5-c]pyrimidine in 60 ml of ethanol was added dropwise 0.82g (8.4 mmole) of concentrated sulfuric acid. The solution was allowed to cool to about 20 C, then diluted to a total volume of 250 ml by the addition of diethyl ether. The mixture was stirred for one hour, and the solid was then separated by filtration. The solid was washed with ether and dried to provide white solid 2,5-diethyl-7-[4- [1-oxothiomorpholino]-1,2,4-triazolo[1,5-c]pyrimidine bisulfate, m.p. 210-2120C. Analysis: Calculated for C13H19N5OS.H2SO4: %C, 39.9; %H 5.4; %N, 17.9; Found: %C, 39.9; ZH, 5.4; %N, 18.2

Claims: Claims: 1. A compound of the formula: EMI80.1 wherein R3 is hydrogen or lower alkyl; one of R5 and R7 is the heterocyclic substitjent EMI80.2 wherein X is oxygen, sulfur, sulfinyl, sulfonyl, methylene, imido or N-lower alkylimido; when R5 is said heterocyclic substituent, R7 is hydrogen or lower alkyl; when R7 is said heterocyclic substituent, Rg is hydrogen, lower alkylthio, phenyl or lower alkyl; and R8 is hydrogen, phenyl or lower alkyl; or a pharmaceutically acceptable salt thereof. 2. A compound of the formula: EMI80.3 wherein R2 is hydrogen or lower alkyl; at least one of R5 and R7 is EMI80.4 wherein each X is independently oxygen, sulfur, sulfinyl, sulfonyl, methylene, imido or lower N-alkylimido; one of R5 and R7 may also be hydrogen or lower alkyl; and R8 is hydrogen, lower alkyl or phenyl; or a pharmaceutically acceptable salt thereof. 3. A compound according to either of claims 1 and 2, wherein X is sulfur or oxygen. 4. A compound according to claim 3 wherein R8 is hydrogen. 5. A compound according to claim 1, selected from the group consisting of: 3,5-bis(n-propyl)-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c]- pyrimidine, 5-ethyl-3-methyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c3- pyrimidine, 3-methyl-5-methylthio-8-phenyl-7-(4-thiomorpholino)-1,2,4 triazolo [4,3-c] pyrimidine, 5-ethyl-3-isopropyl-7-(4-thiomorpholino)-1,2,4-triazolo [4,3-c]pyrimidine, 3-ethyl-5-methyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c3- pyrimidine, 3,5-bis(n-propyl)-7-(4-morpholino)-1,2,4-triazolo[4,3-c]- pyrimidine, 3,5-diethyl-7-(1-piperidino)-1,2,4-triazolo[4,3-c] pyrimidine, 3-isopropyl-7-(4-morpholino)-5-n-propyl-1,2,4-triazolo [4, 3-c]pyrimidine, 7-(4-morphoLino)-5-methylthio-1,2,4-triazolo[4,3-c]- pyrimidine, 3-ethyl-5-n-propyl-7-(4-thiomorpholino)-1,2,4-triazolo- [4,3-c]pyrimidine, 7-(4-methyl-1-piperazino)-5-(n-propyl)-1,2,4-triazolo[4,3-c] pyrimidine, 5-n-propyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c3- pyrimidine, 5-ethyl-7-(4-morpholino)-1,2,4-triazolo[4,3-c]pyrimidine, 5-ethyl-2-methyl-7-(4-morpholino)-1,2,4-triazolo[4,3-c] pyrimidine, and 3,5-diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c] pyrimidine. 6. A compound according to claim2 , selected from the group consisting of 2-methyl-5-(4-thiomorpholino)-1,2,4-triazolo[1,5-c] pyrimidine, 2-ethyl-7-methyl-5-(4-thiomorpholino3-1, 7.,4-triazolo- (1,5-c)pyrimidine, 5,7-bis(4-morpholino)-1,2,4-triazolo[1,5-c]pyrimidine, 5-(1-morpholino)-7-(4-thiomorpholino)-1,2,4-triazolo- [1,5-c]pyrimidine, 2-ethyl-5-methyl-7-(4-thiomorpholino)-1,2,4-triazolo [1,5-cipyrimidine, 2-ethyl-5-methyl-7-(4-morpholino)-1,2,4-triazolo[1,5-c] pyr imidine, 2,5-diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c] pyrimidine, 2-ethyl-7-(4-morpholino)-5-n-propyl-1,2,4-triazolo[1,5-c] pyrimidine, 7-(4-morpholino)-5-n-propyl-1,2,4-triazolo[1,5-c]pyrimdine, 2-ethyl-5-n-propyl-7-(4-thiomorpholino)-1,2,4-triazolo [1,5-c]pyrimidine, 5-n-propyl-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c] pyrimidine, 5-ethyl-7-(4-morpholino)-l ,2 ,4-triazolo[l,S-c]pyrimidine, 5-ethyl-2-methyl-7-(4-morpholino)-1,2,4-triazolo[1,5-c] pyrimidine, 2,5-diethyl-7-(4-morpholino)-1,2,4-triazolo[1,5-c] pyrimidine, 2,5-diethyl-7-[4-(1-dioxothiomorpholino)-1,2,4-triazolo t1,5-c]pyrimidine, and 2,5-diethyl-7-[4-(1-oxothiomorpholino)]-1,2,4-triazolo [1,5-c]pyrimidine. 7. A pharmaceutical composition comprising an effective amount of a compound according to either of claims 1 or 2 and a pharmaceuticaily acceptable vehicle. 8. A compound according to either of claims 1 and 2 for use in obtaining bronchodilation in a rnanrnal. 9. A process for preparing a triazolo[1,5-c]- pyrimidine of the formula EMI83.1 wherein R2 is hydrogen or lower alkyl; R5 is hydrogen, lower alkyl or phenyl; R8 is hydrogen, lower alkyl or phenyl; and X is oxygen, sulfur, sulfinyl, sulfonyl, methylene, imido, or N-lower alkylimido; comprising heating a triazolo[4,3-c]pyrimidine of the formula EMI83.2 wherein R2 t R5, R8 and X are as defined above, in the presence of an aqueous acid to provide said triazolo [1 ,5-c]pyrimidine. 10. A process for preparing a triazolo[l,5e] pyrimidine of the formula EMI84.1 wherein R2 and R7 are each hydrogen or lower alkyl; R8 is hydrogen, lower alkyl or phenyl; and X is oxygen, sulfur, sulfinyl, sulfonyl, methylene, imido, or N-lower alkylimido; corrprising heating a triazolo[4,3-c]pyrimidine of the formula EMI84.2 wherein R2 R7 and R8 are as defined above in the presence of an excess of a heterocyclic amine of formula EMI84.3 wherein X is as defined above to provide said triazolo[1,5-c] pyrimidine 1. A process for preparing a triazolotl,S-cl- pyrimidine of the formula EMI85.1 wherein R2 is hydrogen or lower alkyl; R5 is hydrogen, lower alkyl or phenyl; R8 is hydrogen, lower alkyl or phenyl; and X is oxygen, sulfur, sulfinyl, sulfonyl, methylene, imido, or N-lower alkylimido; comprising heating a triazolo[4,3-clpyrimidine of the formula EMI85.2 wherein R2, R5, R8 and X are as defined above, in the presence of an aqueous acid to provide said triazolo [1 ,5-cipyrimidine. 2. A process for preparing a triazolo [1 , 5-c] pyrimidine of the formula EMI85.3 wherein R2 and R7 are each hydrogen or lower alkyl; R8 is hydrogen, lower alkyl or phenyl; and X is oxygen, sulfur, sulfinyl, sulfonyl, methylene, irnido, or N-lower alkylimido; conprising heating a triazolo[4,3-c]pyrimidine of the formula EMI86.1 wherein R2 R7 and R8 are as defined above in the presence of an excess of a heterocyclic amine of fonrula EMI86.2 wherein X is as defined above to provide said triazolo[1,5-c] pyrimidine

Inventors: WADE, JAMES J.
Applicants: RIKER LABORATORIES, INCORPORATED
Application year: 1984
Main classification: C07D487
IPC codes: C07D239, C07D487