4-PHENYL AND 5-PHENYL-1,4,5,6-TETRAHYDROPYRIMIDINE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING SAID DERIVATIVES, AND PROCESS FOR PREPARING SAID DERIVATIVES

Abstract: Compounds represented by the formula wherein A is H, R- or RO- where R is alkyl of one through six carbon atoms; X is hydrogen, fluoro, chloro, bromo, iodo, hydroxy, alkoxy of one through four carbon atoms, benzyloxy, alkyl of one through four carbon atoms, alkylthio of one through four carbon atoms, alkylsulfinyl of one through four carbon atoms, alkylsulfonyl of one through four carbon atoms or trif­ luoromethyl; and Y is hydrogen or is the same as X; and R¹ is hydrogen or alkyl of one through four carbon atoms; the phenyl substituent carrying the X and Y is at the 4- or 5-position of the tetrahydropyrimidine ring when R¹ is hyd­ rogen or is at the 5-position when R¹ is alkyl; and the phar­ maceutically acceptable salts thereof. These compounds are pharmaceutically useful for treat­ ing depression, anxiety, convulsions, centrally-induced skeletal muscle spasm and spasticity.

Description: 4-Phenyl and 5-Phenyl-1,4,5,6-tetrahydropyrimidine derivatives, pharmaceutical compositions containing said derivatives, and process for preparing said derivatives. BACKGROUND OF THE INVENTION Field of the Invention This invention relates to 1,4,5,6-tetrahydro pyrimidines which are substituted at the 4, 5 or 6 position with a phenyl or substitued phenyl and at the 2 position with an amino, alkylcarbonylamino or alkoxy carbonylamino and the pharmaceutically acceptable salts thereof. The compounds can be combined with suitable pharmaceutical excipients to prepare pharmaceutical compositions which are useful for treating disorders of the central nervous system. The invention further relates to methods of preparing the compounds of the invention. Prior Art A general discussion of psychotic disorders and the use of psychotroptic drugs can be found in the Phar macological Basis of Therapeutics, 4th Edition, L.S. Goodman and A. Gilman, Editors, McMillan Company, New York (1970). It is known that certain 2-amino-4-aryl-2 imidazolines show antihypertensive activity. (See Journal of Medicinal Chemistry, Vol. 16, No. 8, p. 901 (1973)). It is also known that certain 4,5-dihydro-5 phenyl-2-lower alkoxycarbonylaminoimidazoles, the substituted phenyl derivatives thereof, and the n-alkyl derivatives are useful for treating disorders of the central nervous system. See for example U.S. Patents 4,088,771 to Roszkowski et al and U.S. 4,129,661 to Roszkowski, et al. U.S. Patents 3,895,112 and 3,707,560 both to DeAngelis and Hess disclose 4-amino-6-aryl-pyrimidines which are useful as muscle relaxants, bronchodilators, and/or platelet aggregation inhibitors. Also, U.S. 2,735,225 to Goodhue and Mahan of Phillips Petroleum describes certain pyrimidines, for example, 4-phthalimido-2,6-dimethylpyrimidine, which are useful as plant growth regulators. It is also known that certain tetrahydropyrimidines, such as l-methyl-2- (2-thienyl- ethenyl)-tetrahydropyrimidine, are useful as anthelmintic agents used in veterinary practice. See, for example, Organic Chemistry of Drug Synthesis, Lednicer and Uitscher, pp. 266-267, John Wiley and Sons (1977). An entirely new group of tetraphydropyrimidines has now been discovered which is useful in the treatment of disorders of the central nervous system. SUMMARY OF THE INVENTION The broadest aspect of this invention includes compounds of the invention represented by the formula EMI2.1 wherein A is hydrogen, RC(O)- or ROC(O)-; R is alkyl of one through six carbon atoms; Rlis hydrogen or alkyl of one through six carbon atoms; X is fluoro, chloro, bromo, iodo, alkoxy of one through four carbon atoms, benzyloxy, hydroxy, alkyl of one through four carbon atoms, alkylthio of one through four carbon atoms, alkyl sulfinyl of one through four carbon atoms, alkyl sulfonyl of one through four carbon atoms, trifluoromethyl or hydrogen; Y is hydrogen or is the same as X, and the phenyl substituent carrying the X and Y is at the 4 or 5 position of the tetrahydropyrimidine ring when R1 is hydrogen or is at the 5position when R1 is alkyl. Pharmaceutically acceptable salts of the above compounds are also encompassed within the scope of the invention. Another aspect of the invention is a pharmaceutical composition which comprises a compound chosen from those represented by Formula I or a pharmaceutically acceptable salt thereof along with a suitable pharmaceutical excepient. Still another aspect of the invention is the administration of a compound of the invention to an animal to treat disorders of the central nervous system, for example, depression, anxiety, convulsions, centrally induced skeletal muscle spasm and spasticity. The invention further relates to a process of preparing the compounds of the invention represented by Formula (I) by converting the appropriate, substituted diamine to the 2-amino-4-phenyl (or 5-phenyl)-1,4,5,6tetrahydropyrimidine. This, in turn, can be converted to the corresponding 2-alkoxycarbonylamino compound or the 2-alkylcarbonylamino compound. Alternatively, the diamine can be converted directly to the 2-alkoxycarbonylamino compound. A more complete discussion of the preferred embodiments is found hereinafter. DETAILED DESCRIPTION COMPOUNDS A subgroup of the broadest aspect of this invention includes the compounds represented by Formula (I) wherein A is hydrogen, RC(O)- or ROC(O)-; R is methyl or ethyl; R1 is hydrogen, methyl or ethyl; X is hydrogen, fluoro, chloro, methoxy, ethoxy, methyl, ethyl or hydroxy; Y is hydrogen or the same as X; and the pharmaceutically acceptable salts thereof. The broadest aspect of the invention can be further subdivided into subgroups such as amines, as shown in Formula (I I), amides as shown in Formula (III), or carbamates as shown in Formula (To). The amines of this invention include the group compounds represented by the formula EMI4.1 wherein X is fluoro, chloro, bromo, iodo, alkoxy of one through four carbons atoms, benzyloxy, hydroxy, alkyl of one through four carbon atoms, alkylthio of one through four carbon atoms, alkyl sulfinyl of one through four carbon atoms, alkyl sulfonyl of one through four carbon atoms, trifloromethyl or hydrogen; Y is hydrogen or is the same as X; R1 is hydrogen or alkyl of one through six carbon atoms; the phenyl substituent carrying the X and Y is at the 4- or 5-position of the tetrahydropyrimidine ring when R1 is hydrogen or is at the 5-position when R1 is alkyl; A preferred subgroup of this class of compounds includes the compounds represented by Formula (II) wherein X is fluoro, chloro, methoxy, ethoxy, hydroxy, methyl, ethyl or hydrogen; Y is hydrogen or is same as X; and R1 is hydrogen, methyl or ethyl. Of the preferred subgroup, the compounds wherein X is fluoro, chloro or hydrogen; Y is hydrogen or the same as X; and R1 is hydrogen or methyl are particularly preferred. The most particularly preferred is the compound where X, Y and R1 are each hydrogen. Typical specific illustrations of the amines of this invention are set forth in the Examples hereafter. The amides of this invention include the compounds represented by the formula EMI5.1 wherein X is fluoro, chloro, bromo, iodo, alkoxy of one through four carbon atoms, benzyloxy, hydroxy, alkyl of one through four carbon atoms, alkylthio of one through four carbon atoms, alkylsulfinyl of one through four carbon atoms, alkylsulfonyl of one through four carbon atoms, trifluoromethyl or hydrogen; Y is hydrogen or is the same as X; R is alkyl of one through six carbon atoms; R1 is hydrogen or alkyl of one through six carbon atoms; and the phenyl substituent carrying the X and Y is at the 4- or 5-position of the tetrahydropyrimidine ring when R1 is hydrogen or is at the 5-position, when R1 is alkyl; A preferred subgroup of this group of compounds includes those represented by Formula (III) wherein X is flouro, chloro, methoxy, ethoxy, hydroxy, methyl, ethyl or hydrogen; Y is hydrogen or is the same as X; R is methyl or ethyl; and R1 is hydrogen, methyl or ethyl. Of the preferred subgroup, those compounds particularly preferred include the compounds of Formula (III) wherein X is fluoro, chloro or hydrogen; Y is hydrogen or is the same as X; R1 is hydrogen or methyl and R is methyl. Typical specific illustrations of the amides of this invention are set forth in the Examples hereafter. The carbamates of this invention are represented by the compounds of the Formula EMI6.1 wherein X is fluoro, chloro, bromo, iodo, alkoxy of one through four carbon atoms, benzyloxy, hydroxy, alkylthio of one through four carbon atoms, alkylsulfinyl of one through four carbon atoms, alkylsulfonyl of one through four carbon atoms, trifluoromethyl or hydrogen; Y is hydrogen or is the same as X; R is alkyl of one through six carbon atoms, R1 is hydrogen or alkyl of one through six carbon atoms; and the phenyl substituent carrying the X and Y is at the 4- or 5-position of the tetrahydropyrimidine ring when R1 is hydrogen or is at the 5-position, when R1 is alkyl. A preferred subgroup of this group of compounds includes those represented by Formula (IV) wherein X is fluoro, choloro, methoxy, ethoxy, hydroxy, methyl, ethyl or hydrogen; Y is hydrogen or is the same as X; R1 is hydrogen, methyl or ethyl; and R is alkyl of 1-3 carbons. Of this subgroup, those particularly preferred are the compounds represented by Formula (IV), wherein X is fluoro, chloro, methoxy, ethoxy, methyl, ethyl or hydrogen; Y is hydrogen or is the same as X; R1 is hydrogen, methyl or ethyl; and R is methyl or ethyl. The most particularly preferred are those compounds where X and Y are both hydrogen, R1 is hydrogen or methyl and R is methyl, ethyl, propyl or isopropyl. Typical specific illustrations of the carbamates of this invention are set forth in the Examples hereafter. The compounds of this invention are optionally substituted at the l-position of the tetrahydropyrimidine ring with an alkyl group; at the 2-position with an amino (No2), an alkyl carbonylamino (-NHC(O)R) or alkoxycarbonylamino (-NHC(O)OR); and at the 4- or 5position with a phenyl or substituted phenyl. Where the phenyl substitution is at the 5-position with no substitution at the l-position, the compounds are not optically active because of tautomerism, i.e. there is an equilibrium between the two linkage isomers. However, once the position of the double bond is fixed by the alkyl substitution at the l-position, the compounds are optically active due to the asymmetrical atom at the five position. If on the other hand, the phenyl is substituted at the 4-position, the compounds of the invention. have an asymmetric carbon atom at the 4-position of the tetrahydropyrimidine ring and thus exist as optically active enantiomers, i.e. (+) and (-) compounds. The above Formulas (I), (it) , (III) and (IV) are intended to represent the respective individual (+) and (-) optical enantiomers as well as mixtures thereof, and accordingly the individual enantiomers as well as mixtures thereof (e.g. racemic mixtures) are encompassed within the scope of the invention. The compounds of the invention will be named herein, for purposes of convenience, as follows: A. 4-phenyl substituted compounds 2-amino-4-(substituted phenyl)-1,4,5,6-tetra hydropyr imidine; 2-alkylcarbonylamino-4- (substituted phenyl)1,4,5,6-tetrahydropyrimidine; 2-alkoxycarbonylamino-4-(substituted phenyl) - 1,4,5,6-tetrahydropyrimidine; B. 5-phenyl substituted compounds 2-amino-5-(substituted phenyl)-1,4,5,6-tetra hydropyr imid ine; l-alkyl-2-amino-5-(substituted phenyl) 1,4,5,6- tetrahydropyr imidine; 2-alkylcarbonylamino-5-(substituted phenyl) - 1,4,5,6-tetrahydropyrimidine; l-alkyl-2-alkylcarbonylamino-5- (substituted phenyl) - 1,4,5,6-tetrahydropyrimidine; ; 2-alkoxycarbonylamino-5-(substituted phenyl) - 1,4,5,6-tetrahydropyrimidine; l-alkyl-2-alkoxycarbonylamino-5- (substituted phenyl)-1,4,5,6-tetrahydropyrimidine; Also included within the scope of the invention are pharmaceutically acceptable salts of each of the above subgroups compounds. Pharmaceutically acceptable salts include those salts of the parent compound which do not significantly adversely affect the pharmaceutical properties (e.g. toxicity, effectiveness, etc.) of the parent compound and are conventionally used in the pharmaceutical art. The pharmaceutically acceptable salts of the present invention are pharmaceutically acceptable hydrogen-anion addition salts of the compounds of Formula (I), (II), (III) and (IV). Suitable pharmaceutically acceptable hydrogenanion addition salts include (expressed with respect to the anion), for example, inorganic salts such as, for example, chloride, bromide, iodide, sulfate, phosphate, nitrate, and the like, or organic salts such as, for example, acetate, benzoate, lactate, propionate, butyrate, valerate, tartrate, maleate, fumarate, citrate, succinate, tosylate, ascorbate, palmitate, glyconate, adipate, and the like. The preferred pharmaceutically acceptable salts are the hydrochloride, hydrobromide, nitrate, maleate and citrate, and correspondingly the preferred and particularly preferred salts are the corresponding salts of the groups of the preferred and particularly preferred compounds described above. Utility and Administration The compounds of the invention are useful as agents for treating, palliating, or preventing undesirable conditions, in mammals, involving the central nervous system such as depression, anxiety, convulsions, centrally induced skeletal muscle spasms or spasticity disorders. Thus, the compounds of the invention are useful as antidepressants, anxiolytic agents, anticonvulsants, antispasmotics, or antispasticity agents. Preferably, the compounds are used as antidepressants. Initial determination of the spectrum of psychotropic activity, in mammals, for a given compound is obtained by applying routine experimental procedures. Antidepressant activity is initially determined using the methods discussed in Askew, Life Sciences, Vol. 2, p. 725 (1963) and Vernier et al, Fed. Proc., Vol. 21, p. 419 (1962). Depressant or tranquilizing activity (antianxiety agent) is initially determined using methods discussed by Irwin in Animal and Clinical Pharmacological Technique in Drug Evaluation edited by J. H. Nodine et al, pp. 36-54, Year Book Medical Publishers, Inc., Chicago (1964). For anticonvulsant activity the method used is described by Swinyard, J. of Amer. Phar. Assoc., Scientific Edition, Vol. 38, p. 201 (1949). For centrally acting skeletal muscle relaxant activity based on polysynaptic transmission inhibition (antispasmotic) the method used is set forth in King and Unna, "The Action of Mephenesin and Other Interneuron Depressants on the Brain Stem", J. Pharmacol. Exp. Ther., Vol. 111, p. 293 (1954); Barnett and Fiore, European Journal of Pharmacology, Vol. 13, p. 239 (1971); Kamijo and Koelle, Proceedings of the Society for Experimental Biology and Medicine, Vol. 88, pp. 565-568 (1955). In general, the dosage will be an amount effective to achieve the desired results. The preferred dosage depends upon the particular subject and disorder being treated and can vary within wide limits such as, for example, between 0.001 and 50 mg. per kg. of body weight per day, preferably between 0.01 and 10 mg/kg. Generally, where the compounds are administered as antidepressants, they can be administered in the same manner as imipramine and preferably are administered at a rate of less than about 10 mg/kg per day and preferably less than 5 mg/kg. Where the compounds are administered as anticonvulsants, they are best administered prophylactically to prevent or reduce the occurrence and/or severity of convulsions in mammals which are subject to convulsions which are etiopathic to the central nervous system. Generally, under the usual conditions for which the compounds of this invention are administered, there are no adverse toxic effects. The compounds can be administered orally, rectally or parenterally (for example, by intravenous, intraperitoneally or intramuscular injection). The compounds are typically administered as pharmaceutical compositions comprising an effective amount of at least one compound of the invention and at least one suitable pharmaceutical excipient. An effective amount is that amount which gives the desired effect in the mammal that is being treated. The level of the drug in the formulation can vary from 0.1 percent weight (%w) to 99%w or more of the drug based on the total formulation and about 18w to 99.9%w excipient. Preferably the drug is present at a level of l%w-95%w. Where the compounds are administered parenterally, they will, of course, be administered in liquid dosage forms, whereas when administered orally or rectally, they can be administered in either solid or liquid forms. Typically, the dosage forms comprise the compound and a pharmaceutically acceptable excipient such as a carrier, preferably formulated in unit dosage form to facilitate the simple administration of precise dosages. The dosage form can optionally contain other compatible medicaments and excipients such as preservatives, emulsifying agents and wetting agents and buffering agents. Liquid dosage forms include, for example solutions, suspensions, emulsions, syrups, elixirs, etc. Liquid carriers include, for example, water, saline solution, etc. Solid dosage forms include, for example, tablets, powders, capsules, pills, etc. Suitable solid carriers include, for example, pharmaceutical grades of starch, lactose, sodium saccharin, sodium bisulfite and the like, and conventional suppository carriers, e.g. polyethylene glycol, polysorbate, stearic acid, diglycol stearate, carbowax, etc. Thus, the compounds may be prepared as pills such as capsules or tablets each having about 10-200 mg per pill. The compounds of this invention are contraindicated in patients who have shown a prior sensitivity to them. If the new compounds are to be combined with other psychotropic agents, careful consideration should be given to the pharmacology of the agents to be employed. The compounds of this invention can be combined with chemically and pharmacologically compatible tranquilizers (e.g. perphremazine) or anxiolytic agents (e.g. librium). Definitions The following terms, as used hereinabove and below, have the following meaning unless expressly stated to the contrary. The term alkyl includes both straight chain and branched chain alkyls having the number of carbon atoms indicated. For example alkyl of one through four carbon atoms include, for example, methyl, ethyl, n-propyl, isopropyl, t-butyl, n-butyl and the like. Alkyl of one through six includes the foregoing as well as amyl, hexyl and the like. The term alkoxy of one through four carbon atoms can be defined as the group OR' wherein R' is alkyl of one through four carbon atoms. The term "room temperature" or "ambient temperature" refers to about 200 Centigrade and all temperatures and temperature ranges refer to degrees Centigrade. All percents refer to weight percents and the term equivalent mole amount refers to an amount stoichiometrically equivalent to the other reactant in the reaction referred to. Process of the Invention A. 5-Phenyl-1,4,5,6-tetrahydropyrimidines The symmetrical compounds of this invention, namely, the 5- (optionally substituted phenyl)-1,4,5,6- tetrahydropyrimidines, are prepared by converting a suitable propane diamine of Formula (D) in Reaction Sequence 1 to the 2-aminotetrahydropyrimidine of Formula (Ill), or the carbamate of Formula (IV1). The aminotetrahydropyrimidine (Il1) is converted to the carbamate (IV1) or the amide of Formula (III1). REACTION SEQUENCE 1 EMI13.1 The overall process is set forth in Reaction Sequence 1 using as the starting material an appropriately substituted benzyldehyde of Formula A, where X and Y are as hereinbefore defined. Where X is hydroxy, however it is preferably first converted to benzyloxybenzaldehyde which is reacted as shown in Reaction Sequence 1 and finally the benzyloxy is converted to the hydroxy by hydrogenolysis. The benzaldehyde Formula (A) is reacted with cyanoacetic acid at a temperature of from about 300C to about 1200C in a suitable solvent. Preferably the temperature is from about 500C to about 1000C. The solvent can be any solvent in which the reaction readily takes place but is preferably a cyclic amine such as pyridine. Also present is a small amount of a stronger base such as morpholine, piperidine, piperazine, diazabicyclononine, etc. Preferably this base is piperidine. The cyanoacetic acid reacts with the benzaldehyde according to the principles discussed in Chem. Ber., Vol. 95, pages 195-198, (1962), by Chiemenz and Engelhard. That reference is incorporated herein by reference. The product of this reaction is the corresponding phenylglutaronitrile shown in Reaction Sequence 1 as Formula (B). The compound of Formula (B) is then treated with an aqueous acid to form the corresponding 3-phenylglutaramide of Formula (C). The acid may be any suitable inorganic mineral acid such as hydrochloric or sulfuric. Preferably sufuric acid is employed. This reaction can be carried out at temperatures from about 50C to about 50 C, but is preferably carried out at about room temperature. Once the reaction is complete, excess acid is neutralized with a suitable base such as ammonium hydroxide and the resulting solid precipitate is collected by filtration, centrifugation or the like. Alternatively, any other known methods of formation of amides from nitriles can be employed. For example, refluxing the nitrile of Formula (B) with aqueous base results in the corresponding amide. The addition of hydrogen peroxide accelerates the hydration of nitriles in alkaline solutions, thus hydrogen peroxide with a suitable base such as sodium carbonate, sodium hydroxide, potassium'hydroxide, magnesium hydroxide or the like can be used with success. This is further discussed in Organic Chemistry, 2nd Ed., Cram and Hammond, p. 307, McGraw Hill Book Company, 1964. In addition the process may be performed by adapting the method described by Murray and Cloak in Journal of the American Chemical Society, Vol. 56, pages 2749-2751 (1934). These references are incorporated herein by reference. The amide of Formula (C) in turn is readily converted into the 2-phenyl-1,3-propanediamine of Formula (D) by adaptation of the Hoffman rearrangement or any of the other known methods for the preparation of amines from amides that proceed with the loss of one carbon, for example, by treatment with lead tetracetate. In the Hoffman rearrangement, the unsubstituted amide is reacted with sodium hypobromite (or aqueous sodium hydroxide and bromine) at low temperatures of -20 to about 100C. The reaction takes place readily at low temperatures of about -10 to about lO0C with increased heating as the reaction progresses, the reaction reaching completion at about 50 to 100 C, preferably 700C. The reaction is discussed in Cram and Hammond's Organic Chemistry, ibid, p. 490 and in S. Simons, J. ORG. CHEM. 38, 414 (1973). The references are incorporated herein by reference. Once the diamine of Formula (D) is obtained it can be converted into the 2-amino-1,4,S,6-tetrahydro pyrimidine compound or Formula (II1) or the 2-alkoxy carbonylamino-l,4,5,6-tetrahydropyrimidine compound. The 2-amino-5-phenyl-1,4,5,6-tetrahydropyrim compounds are prepared by adopting methods known in the art to this particular process. For example, the method set forth in Matier, et al, J. of MED. CHEM. 16, No. 8, 901-908 (1973), has been found to be particularly useful. In this case the diamine as the free base is dissolved in a suitable solvent such as methanol and a solution of cyanogen bromide in an inert solvent such as methanol is added to the solution. Generally the reaction will be complete in less than 5 hours at a temperature of about 100 to about 50 C, preferably about 200 to 300C. This method results in the 2-amino-5-phenyl-1,4,5,6tetrahydropyrimidine hydrobromide which is then crystallized from a suitable solvent such as methanol and isopropylether. This compound is readily converted into the amide by reacting with a suitable acid chloride (R-CO-C1), anhydride (R-co-o-co-R), ester (R-co-OR6) or the acid itself (R-CO-OH) in the presence of an activating agent such as dicyclohexylcarbodiimid or carbonyldiimidazole. Alternatively, a carboxylic acid derivative, for example tetraacyl (C1-C6) glycolrils can be used. For preparations and reactions of tetraacylglycolurils see D. Gulling, Ann. Chem. 1973, 263 and C. Ease and D. Gulling, Ann. Chem. 197f, 95. The 2-alkoxycarbonylamino-5-phenyl-1,4,5,6-tetra- hydropyrimidine is readily prepared by adapting known methods to the particular compounds at hand. See for example U.S. 4,088,771 to Roszkowski et al, which is incorporated herein by reference. The diamine of formula (D) is reacted with a compound represented by the formulas EMI16.1 where Z is hydrogen or COOR, R is lower alkyl of one through six carbon atoms and R2 is alkyl of one through five carbon atoms. This reaction can be conveniently effected by treating the diamine of Formula (D), or typically an acid salt thereof (e.g. the dihydrochloride salt), with the starting material of formula L or L' having the desired R substituent, in a suitable solvent. Typically, the reaction is conducted under alkaline to slightly acid conditions, preferably essentially neutral. Where an acid salt of the diamine of Formula (D) is used, a sufficient amount of an inorganic or organic base is added to the reaction mixture either before or after the addition of one or both of the reactants to neutralize all or part of the acid salt moiety. Suitable bases which can be used include, for example, alkali metal carbonate, or bicarbonates, acetates, for example, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium acetate, alkali metal lower alkoxides, for example, sodium methoxide, potassium methoxide, sodium t-butoxide, lithium methoxide, and the like, alkali metal and alkali earth hydroxides, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, and the like, and mixtures thereof. Suitable organic bases include, for example, pyridine, triethylamine, diazabicyclononane, and the like or mixtures thereof. Conveniently, the solvent in which the reaction is carried out is a mixture of water and one or more inert organic solvents. Suitable inert organic solvents which can be used include, for example, methanol, ethanol, isopropanol, diethyl ether, chloroform, benzene and the like and mixtures thereof. The reaction is carried out at temperatures in the range of about from 10 to 100 C, preferably about from 500 to 75 C, for about from 1/2 hour to 14 days. Typically, a mole ratio of about from 0.5 to 2, preferably about 1 mole of the diamine of Formula (D) is used per mole of starting material of Formula (L) or (L'). However, temperatures, reaction times, and mole ratios both above and below these ranges can be used. Optimum conditions will, of course, vary with the particular reactants and solvents, and can be determined by routine experimentation. The products of Formula (rev) can be separated from the product reaction mixture and further purified by conventional procedures, e.g. filtration, washing, evaporation, crystallization and the like. Non-limiting illustrations of detailed separation and purification procedures can be had by reference to the Examples set forth hereinbelow. The starting materials of Formulas (L) and (L') are known compounds and can be prepared according to known procedures such as those set forth in Japanese Application No. 50012087 or by obvious modifications of such procedures. The compounds of Formula (C) can be used either as the respective mono- (Z is H) or bis- (Z is COOR) or as a mixture of the mono- and bis- compounds. Conveniently, the compound of Formula (L) is prepared as a mixture of the mono- (Z is H) and bis (Z is COOR) and the mixture then used in the aforedescribed reaction without separation of the mono- and bis- products. In a further process embodiment, the compounds of the invention represented by Formula (IV1) are prepared by treating the diamine of Formula (D) with a compound of the general formula EMI18.1 wherein R is as defined hereinabove and M and P independently are chlorine, lower alkoxy or lower alkylthio. The term lower alkoxy or lower alkylthio refers to alkoxy or alkylthio groups having an alkyl group from one through six carbon atoms which may be branched or straight chain attached to an oxygen or sulfur atom. The reaction preferably is carried out in the presence of a suitable organic or inorganic base, such as triethylamine, pyridine, sodium hydroxide, sodium bicarbonate, or'sodium carbonate at 0 to 1000C, preferably at 0 to 50 C. If one of M or P is halogen and the other of M or P is lower alkoxy or lower alkylthio the reaction is first started in the presence of a base and completed at a pH of 2 to 8 between 0 to 1500C, preferably 200 to 1200C. If both M and P are lower alkoxy or lower alkylthio, the reaction is carried out at O to 1500C, preferably 300 to l200C, optionally in a solvent such as a lower alkanol, acetonitrile diluted acetic acid, ethylene glycol, tetrahydrofurane, dioxane, benzene, toluene, halogenated hydrocarbon, water, or the like. It is advantageous to use solvents which contain water. The pH range should be between 2 and 8 preferably between 2 and 5. The compounds of Formula (L") are known compounds and can be prepared in accordance with the procedures described in German OLS 2438120. In still a further modification the compounds of the invention can be prepared by treating the diamine of Formula (D) with a compound of the general formula ROOC-NHCN wherein R is as defined above. The reaction conditions are the same as applied with the compounds of the Formula (L") with M and P both being lower alkoxy or lower alkylthio. These compounds may also be prepared by methods described in German OLS No. 2438120. In a further embodiment, the compounds of this invention are prepared by reacting the compound of Formula (II') with a carbonate of the formula EMI19.1 wherein R is alkyl of one through six carbon atoms. This reaction can be conveniently effected at a suitable temperature by treating the compound of formula (II), or typically an acid salt thereof, e.g. the hydrobomide salt, with the carbonate having the desired R substituent in an inert solvent or by using an excess of the carbonate as the solvent. A suitable temperature for the reaction will be about 200C to about 1200C, preferably about 7O0C to about 1000C. Typically where an acid salt of compound (II') is used as the starting material, the salt is treated before addition of the carbonate with a sufficient amount of an inorganic or organic base to liberate the free base. Suitable bases which can be used include, for example, alkali metal carbonates, alkali metal lower alkoxides, for example, sodium methoxide, potassium methoxide, sodium t-butoxide, lithium methoxide, and the like, alkali metal and alkali earth hydroxides, for example sodium hydroxide, potassium hydroxide, calcium hydroxide, and the like, and mixtures. thereof. Suitable organic bases include, for example, pyridine, triethylamine, diazabicyclononane, and the like and mixtures thereof. Suitable inert organic solvents which can be used include, for example, toluene, dioxane, and the like and mixtures thereof. The compounds of the invention can also be prepared by reacting the 2-amine of Formula (1 11) with an alkyl chloroformate (C1COOR) having the desired R-alkyl substituent in a suitable inert organic solvent; e.g. acetone. This reaction takes place at about -200C to about 20 C, preferably about -50C to 50C. The 5-phenyl-1,4,5,6-tetrahydropyrimidines of this invention which are substituted with an alkyl at the l-position are prepared from the corresponding N-alkyl2-phenyl-1,3-propanediamine according to Reaction Sequence 2. REACTION SEQUENCE 2 EMI21.1 In Reaction Sequence 2, the starting material, ethylene glycol acetal of atropaldehyde of Formula (E) (a known material, see E. Elkik, Bull. Soc. Chim. Fr, 1968(1), 283) is first hydrolyzed by reacting in a weakly acidic aqueous solvent at temperaures of about 250C to about 1000C, preferably about 65-750C. Any organic or inorganic acid can be used with oxalic acid being preferred. The reaction is carried out in a suitable polar, organic solvent which is miscible with water. The lower alcohols such as methanol, ethanol, isopropanol, and the like are useful, with ethanol being preferred. The hydrolysis can be followed by gas chromatography and is usually complete after about forty minutes at a reaction temperature of 70-800C. The liberated atropaldehyde (F) can be isolated (See E. Elkik, supra) or can be reacted in situ by adding an N-alkylhydrazine directly to the hydrolysis mixture. This latter procedure is preferred to avoid the difficulties inherent in the polymerization of atropaldehyde (see E. Elkik, supra). Once the acetal is hydrolyzed a suitable N-alkylhydrazine is added and reacted at temperatures of about lO0C to about 40 C, preferably ambient temperature. This results in a product represented by Formula'(G) wherein R is alkyl of one through six carbon atoms, depending on the N-alkylhydrazine. For example, N-methylhydrazine, N-ethylhydrazine, N-isopropylhydrazine, N-t-butylhydrazine and N-n-hexylhydrazine results in a compound of Formula (G) wherein R is methyl, ethyl, isopropyl, t-butyl and nhexyl, repectively. The pyrrazoline of Formula (G) is reduced, for example by catalytic hydrogenation, to the N-alkylpropane diamine of Formula (D2). The compound of Formula (D2) is then converted to the amino pyrimidine (112), amide (III2) or carbamate (it2) according to procedures discussed hereinbefore. B. 4-Phenyl-1,4,5,6-tetrahydropyrimidines The preparation of the 2-amino-, 2-amido- or 2-alkoxycarbonylamino-4-(optionally substituted phenyl)-1,4,5,6-tetrahydropyrimidines is shown in Reaction Sequence 3. REACTION SEQUENCE 3 EMI23.1 In this case the starting materials represented by Formula (H) are different but the intermediate steps from the phenylglutaranitrile of Formula (J) are similar to those set forth hereinbefore for the 5-phenyl-1,4,5,6- tetrahydropyrimidines and the reaction conditions for those steps as previously defined apply here. The preparation of the compound of Formula (J) occurs as discussed by R. Bertocchio and J. Dreux, Bull. Soc. Chem. Fr. 1962, 1809-1813. In the preparation of the 2-phenylglutaronitrile of Formula (J) the appropriate phenylacetonitrile of Formula (H) is reacted with acrylonitrile (CH2=CHCN) at temperatures of about 300 to 100 C, preferably under reflux for less than 5 hours. Generally, the phenylacetonitrile will be in substantial molar excess over the acrylonitrile and will act as a solvent for the reaction mixture. However, other solvents which are suitable and inert towards the reaction can be used such as toluene. The mixture that results consists mainly of unreacted phenylacetonitrile (H), phenylglutaronitrile (J) and the pentane tricarbonitrile (K). The three nitriles are separated by vacuum distillation and recrystallization. The 2-phenylglutaronitrile (J) is then converted to the compound represented by Formula (M) which in turn is converted to the diamine of Formula (N) which then is converted to the desired products of Formulas (it3), (III3) or (i;r4), The reaction conditions required to convert the 2-phenylglutaranitrile of Formula (J) to the compounds of this invention are essentially the same as the conditions discussed in the section for the preparation of the 5-substituted 1,4,5,6-tetrahydropyrimidines as discussed before. An alternative route to the preparation of the l-phenyl-1,3-propanediamine is set forth in Reaction Sequence 4. REACTION SEQUENCE 4 EMI25.1 In this sequence, the starting material is the appropriately substituted benzonitrile (0) and the reaction to the B-aminocinnamonitr ile (Q) is essentially as that set forth in Chem. Ber., 82, 254 (1949) by Dornow et al, which is incorporated herein by reference. In this Reaction Sequence, the benzonitrile is reacted with acetonitrile to give the S-aminocinnamonitrile represented by Formula (0) which in turn is reduced to give the l-phenyl-1,3-propanediamine, which is then converted to a compound of Formula (II), (III4), or (IV4) as discussed hereinbefore. The respective optical isomers of formulas II2-II4, III2-III4, and IV2-IV4 can be conveniently prepared by using the corresponding optically active isomer starting material of Formulas (D2), (K), (N), etc. The optically active isomer starting material can be obtained by resolution of the corresponding dl mixture by applying conventional resolution procedures. Note for example the procedure described in Ann. Chem., Vol. 494, page 143 (1932). Also see "Tables of Resolving Agents and Optical Resolutions," Samuel H. Wilen, U. of Notre Dame Press (1972), pp.159-181 and "Stereochemistry of Carbon Compounds" by E. Eliel, McGraw-Hill, 1962, Chap. 4. The pharmaceutically acceptable salts of the compounds of the invention (including Formulas II2-II4, III2-III4, and IV1-IV4 racemic mixtures and separate optical isomers) can be conveniently prepared by treating the corresponding free base of Formula (I), of the invention, with an acid or via other conventional procedures such as, for example, ion exchange. The free base of Formula (I) may be obtained from the pharmaceutically acceptable salt by treating said salt with a conventional organic or inorganic base such as one employed to liberate a free base from the corresponding acid salt as described hereinbefore. Both conversions occur at -20 to 1000C, preferably 5-30 C. A further understanding of the invention can be had from the following non-limiting preparations and examples, wherein, unless stated to the contrary, racemates are used as starting materials and corresponding racemic mixtures are obtained as products. PREPARATION A: 3-phenylglutaronitriles (Reaction Sequence 1) 1. 3- (2,6-dichlorophenyl) glutaronitrile. A solution consisting of 31.5 grams (g) of 2,6-dichlorobenzaldehyde, 39g of cyanoacetic acid and 2.5 milliliters (ml) of piperidine in 100 ml of pyridine is heated on a steambath for 7 hours. The initial rapid evolution of carbon dioxide gradually diminishes over the reaction time. Most of the solvent is removed under reduced pressure and the residue is dissolved in about 400ml of benzene. The solution is washed three times with water, three times with dilute sodium bisulfite, again with water, and finally with saturated sodium bicarbonate. The solvent is removed under vacuum and the residue is recrystallized once from 50ml of methanol and once more from 50ml of isopropanol to give 12.3g of 3-(2,6-dichlorophenyl)glutaronitrile having a melting point (mp) of 104-60C. 2. Similarly, by following in principle the procedure of Part 1 of this Preparation but substituting an appropriate benzaldehyde for 2,6-dichlorobenzaldehyde, other 3-phenylglutaronitriles are prepared such as 3-phenylglutaronitrile, boiling point (bp) 128-1340C at 0.02mm; 3-(2-chlorophenyl)glutaronitrile, bp about 150 C at 0.02mm; 3- (3-chlorophenyl) glutaronitrile; 3-(4-chlorophenyl)glutaronitrile; 3-(2-fluorophenyl)glutaronitrile 3-(3-fluorophenyl)glutaronitrile; 3-(4-fluorophenyl)glutaronitrile, bp 130-1400 at 0.005mm; 3-(2-bromophenyl)glutaronitrile; 3-(3-bromophenyl)glutaronitrile, mp 94-960C; 3-(4-bromophenyl)glutaronitrile; 3-(2-iodophenyl)glutaronitrile; ; 3- (3-iodophenyl) glutaronitrile; 3-(4-iodophenyl)glutaronitrile; 3- (2,3-dichlorophenyl) glutaronitrile; 3-(2,4-dichlorophenyl)glutaronitrile, mp 76-780C; 3- (3,4-dichlorophenyl)glutaronitrile; 3- (3, 5-dichlorophenyl) glutaronitr ile; 3-(2,5-dichlorophenyl)glutaronitrile; 3-(2,3-didifluorophenyl)glutaronitrile; 3-(2,4-difluorophenyl)glutaronitrile; 3-(3,4-difluorophenyl)glutaronitrile; 3-(2,5-difluorophenyl)glutaronitrile; 3-(2,6-difluorophenyl)glutaronitrile; 3- (3,5-difluorophenyl) glutaronitrile; 3-(2,6-dibromophenyl)glutaronitrile; 3-(2,4-dibromophenyl)glutaronitrile; 3-(3,5-dibromophenyl)glutaronitrile; 3-(2,4-diiodophenyl)glutaronitrile; 3-(2,6-diiodophenyl)glutaronitrile; and the like. 3. 3- (3-methoxyphenyl) glutaronitrile. A solution consisting of 25g of m-anisaldehyde, 47g of cyanoacetic acid and 3ml of piperidine in 120ml of pyridine is placed in a suitable reaction vessel and kept in a 1100 oil-bath for 22 hours. Most of the solvent is removed under reduced pressure and the remaining oil is dissolved in about 400ml of toluene. The solution is washed sequentially with equal volumes of water, 10% hydrochloric acid and saturated sodium bicarbonate. The washed solution is then concentrated under vacuum and the residue is distilled to give 20.7g of 3-(3-methoxyphenyl)glutaronitrile, bp 146-153 at O.Olmm. 4. Similarly, by following in principle the procedure of Part 3 of this preparation but substituting other substituted benzaldehydes for m-anisaldehyde, other 3- (substituted phenyl)glutaronitriles can be prepared, such as 3- (2-methoxyphenyl) glutaronitrile; 3- (4-methoxyphenyl) glutaronitrile; 3-(2-ethoxyphenyl)glutaronitrile; 3-(3-ethoxyphenyl)glutaronitrile; 3- (4-ethoxyphenyl) glutaronitrile; 3-(2-propoxyphenyl)glutaronitrile; 3- (3-propoxyphenyl) glutaronitrile; 4- (4-propoxyphenyl) glutaronitrile; 3-(4-butoxyphenyl)glutaronitrile; 3-(2-benzyloxyphenyl)glutaronitrile; 3-(3-benzyloxyphenyl)glutaronitrile; 3-(4-benzyloxyphenyl)glutaronitrile, m.p. 140-143 ; 3-(2-methylphenyl)glutaronitrile; 3-(3-methylphenyl)glutaronitrile; ; 3-(4-methylphenyl)glutaronitrile, bp 124-130 C/0.02mm, 3- (2-ethylphenyl) glutaronitrile; 3-(3-ethylphenyl)glutaronitrile; 3-(4-ethylphenyl)glutaronitrile; 3-(2-isopropylphenyl)glutaronitrile; 3-(3-isopropylphenyl)glutaronitrile; 3-(4-isopropylphenyl)glutaronitrile, bp about 180 C/0.05mm; 3- (2-trifluoromethylphenyl) glutaronitrile 3- (3-trifluoromethylphenyl) glutaronitrile; 3- (4-tr ifluoromethylphenyl) glutaronitr ile; 3- (2-methylthiophenyl) glutaronitr ile; 3-(4-methylthiophenyl)glutaronitrile; 3-(2-ethylthiophenyl)glutaronitrile; 3-(4-ethylthiophenyl)glutaronitrile; 3-(2-butylthiophenyl)glutaronitrile; 3-(3-butylthiophenyl)glutaronitrile; 3- (4-methylsulfinylphenyl) glutaronitrile; 3-(4-ethylsulfonylphenyl)glutaronitrile; 3-(2,4-dimethoxyphenyl)glutaronitrile; ; 3-(2,6-diethoxyphenyl)glutaronitrile; 3- (3,4-dibenzoyloxyphenyl)glutaronitrile; 3-(3,5-diethylthiophenyl)glutaronitrile; 3-(2,6-dimethylsulfinylphenyl)glutaronitrile; 3- (2,6-dimethylsulfonylphenyl)glutaronitrile; and the like. PREPARATION B: 3-Phenylglutaramides (Reaction Sequence 1) 1. 3-(2,6-dichlorophenyl)glutaramide. Twelve and three-tenths (12.3) of 3-(2,6-dichlorophenyl)glutaronitrile, prepared according to Preparation A, Part 1, is dissolved in a mixture of 70ml of concentrated sulfuric acid and 3ml of water. This solution is allowed to stand for 2 days at room temperature and then poured over crushed ice and is neutralized with ammonium hydroxide. The solid precipitate is collected, washed with water and dried under vacuum to give 13.8g of 3-(2,6-dichlorophenyl)glutaramide, mp 221-2250. 2. Similarly, by following the procedure of Part 1 of this preparation but substituting other suitable 3-phenylglutaronitriles (such as those set forth in Preparation A, Parts 2 or 5) for 3-(2,6-dichlorophenyl)glutaronitrile, other corresponding 3-phenylglutaramides are obtained such as 3-phenylglutaroamide, melting point 183-1840C; 3-(2-chlorophenyl)glutaramide, mp 1890C; 3- (3-chlorophenyl) glutaramide; 3- (4-chlorophenyl) glutaramide; 3-(2-fluorophenyl)glutaramide; 3-(3-fluorophenyl)glutaramide; 3-(4-fluorophenyl)glutaramide, mp 194-1960C; 3- (2-bromophenyl) glutaramide; 3- (3-bromophenyl)glutaramide, mp 168-1700C; 3-(4-bromophenyl)glutaramide; 3-(2-iodophenyl)glutaramide; 3-(3-iodophenyl)glutaramide; 3-(4-iodophenyl)glutaramide; ; 3- (2, 3-dichlorophenyl) glutaramide; 3- (2,4-dichlorophenyl)glutaramide, mp 194-1960C; 3-(3,4-dichlorophenyl)glutaramide; 3- (3, 5-dichlorophenyl) glutaramide; 3-(2,5-dichlorophenyl)glutaramide; 3-(2,3-difluorophenyl) glutaramide; 3-(2,4-difluorophenyl)glutaramide; 3-(3,4-difluorophenyl)glutaramide; 3-(2,5-difluorophenyl)glutaramide; 3-(2,6-difluorophenyl)glutaramide; 3- (3, 5-difluorophenyl) glutaramide; 3-(2,6-dibromophenyl)glutaramide; 3-(2,4-dibromophenyl)glutaramide; 3-(3,5-dibromophenyl)glutaramide; 3-(2,4-diiodophenyl)glutaramide; 3-(2,6-diiodophenyl)glutaramide; and the like. 3. 3- (3-methoxyphenyl) glutaramide. A sample of 18.7g of 3-(3-methoxyphenyl)glutaronitrile prepared according to Preparation A, Part 3, is dissolved in 250ml of acetone. This solution is stirred in an ice-bath and added are 125ml of water, 40ml of 30% hydrogen peroxide and 25ml of 10% sodium carbonate. The mixture is allowed to stand at room temperature overnight and is then concentrated to a volume of about 125ml. The residue is cooled and the resulting crystalline precipitate is collected, washed with water and dried under vacuum to give 17.4g of 3-(3-methoxyphenyl)glutaramide, mp 161-162 . 4. Similarly, by following in prinicple the procedure of Part 3 of this preparation, but substituting other suitable 3-phenylglutaramides prepared according to the process of Preparation A, Part 4, other corresponding 3- (substituted phenyl)glutaramides are prepared such as 3- (2-methoxyphenyl) glutaramide; 3- (4-methoxyphenyl) glutaramide; 3-(2-ethoxyphenyl)glutaramide; 3-(3-ethoxyphenyl)glutaramide; 3-(4-ethoxyphenyl)glutaramide; 3-(2-propoxyphenyl)glutaramide; 3-(3-propoxyphenyl)glutaramide; 3-(4-propoxyphenyl)glutaramide; 3-(4-butoxyphenyl)glutaramide; 3-(2-benzyloxyphenyl)glutaramide; 3-(3-benzyloxyphenyl)glutaramide; 3-(4-benzyloxyphenyl)glutaramide, m.p. 205-2070C; 3- (4-methylphenyl)glutaramide, bp 194-1960C; 3-(2-methylphenyl)glutaramide; ; 3-(3-methylphenyl)glutaramide; 3- (3-ethylphenyl) glutaramide; 3-(4-ethylphenyl)glutaramide; 3-(2-ethylphenyl)glutaramide; 3-(2-isopropylphenyl)glutaramide; 3-(3-isoproplphenyl)glutaronitrole; 3-(4-isopropylphenyl)glutaramide, bp 192-1930C; 3- (2-tr ifluoromethylphenyl) glutaramide; 3-(3-trifluoromethylphenyl)glutaramide; 3-(4-trifluoromethylphenyl)glutaramide; 3-(2-methylthiophenyl)glutaramide; 3-(4-methylthiophenyl)glutaramide; 3-(2-ethylthiophenyl)glutaramide; 3-(4-ethylthiophenyl)glutaramide; 3-(2-butylthiophenyl)glutaramide; 3-(3-butylthiophenyl)glutaramide; 3-(4-methsulfinylphenyl)glutaramide; 3- (4-ethylsulfonylphenyl) glutaramide; 3-(2,4-dimethoxyphenyl)glutaramide; 3-(2,6-diethoxyphenyl)glutaramide; ; 3-(3,4-dibenzyloxyphenyl)glutaramide; 3-(3,5-diethylthiophenyl)glutaramide; 3- (2, 6-dimethylsulfinylphenyl) glutaramide; 3- (2, 6-dimethylsulfonylphenyl) glutaramide; and the like. PREPARATION C: 2-Phenyl-1,3-propanediamine (Reaction Sequence 1) 1. 2- (3-methoxyphenyl) -1, 3-propanediamine. A sodium hypobromite solution is prepared from 27g of sodium hydroxide and 23g of bromine in 200ml of water at -30. 15.2G of 3-(3-methoxyphenyl)glutaramide (prepared according to Preparation B, Part 1) are added in five equal portions to the sodium hypobromite solution. The mixture is stirred at OOC until there is a clear solution and is then stirred at room temperature for 1 hour and finally at 700 for 30 minutes. It is cooled and extracted with twelve 70ml portions of methylene chloride and with two 70ml portions of toluene. The combined extracts are dried over sodium sulfate, concentrated and distilled to yield 5.lg of 2-(3-methoxyphenyl)-1,3-propanediamine, bp 140 C at lmm. A small amount of the dihydrochloride salt is prepared by dissolving a few drops of the diamine in ethanol hydrogen chloride and adding ether to the resulting solution to crystallize the dihydrochloride of 2-(3-methoxyphenyl)-1,3-propanediamine, mp 232-2340. 2. Similarly, by following in principle the procedure of Part 1 of this preparation but substituting other suitable 2-phenylglutaramides prepared according to Preparation B, Parts 2, 3, or 4 for 3-(3-methoxyphenyl)glutaramide, other 2-phenyl-1,3-propanediamines are prepared, such as 2-phenyl-1,3-propanediamine, bp 85-870C/2mm (as dihydrochloride [diHCl] salt, mp 258-2620C); 2- (2-chlorophenyl) 1,3-propanediamine, bp 87-920C/O.05 mm (di HC1 salt, mp 253-2570C); 2-(3-chlorophenyl)l,3-propanediamine; 2- (4-chlorophenyl) 1,3-propanediamine; 2- (2-fluorophenyl) -1, 3-propanediamine; 2- (3-fluorophenyl) -1, 3-propanediamine; 2- (4-fluorophenyl)-1,3-propanediamine, (diHC1 salt mp 292.5-2950C); 2-(2-bromophenyl)-1,3-propanediamine; 2-(3-bromophenyl)-l,3-propanediamine, bp 120-1250C/0.02 mm (diHCl salt, mp 260-2650C); 2- (4-bromophenyl) -1, 3-propanediamine; 2-(2-iodophenyl)-1,3-propanediamine; 2-(3-iodophenyl)-1,3-propanediamine; 2-(4-iodophenyl)-1,3-propanediamine; 2-(2,3-dichlorophenyl)-1,3-propanediamine; 2- (2,4-dichiorophenyl) -1,3-propanediamine, bp 1100C/0.01 mm (diHCl salt, mp 268-270 C; 2- (3,4-dichlorophenyl) -1, 3-propanediamine; 2- (3,5-dichlorophenyl)-1,3-propanediamine; ; 2- (2,5-dichlorophenyl)-l, 3-propanediamine; 2-(2,6-dichlorophenyl)-1,3-propanediamine, bp 126-1280C/0.5 mm (dipicrate salt, mp 253-2550C); 2- (2,3-difluorophenyl) -1,3-propanediamine; 2-(2,4-difluorophenyl)-1,3-propanediamine; 2-(3,4-difluorophenyl)-1,3-propanediamine; 2- (2,5-difluorophenyl) -1,3-propanediamine; 2- (2,6-difluorophenyl) -1,3-propanediamine; 2- (3,5-difluorophenyl)-1,3-propanediamine; 2-(3,6-dibromophenyl)-1,3-propanediamine; 2-(2,4-dibromophenyl)-1,3-propanediamine; 2-(3,5-dibromophenyl)-1,3-propanediamine; 2-(2,4-diiodophenyl)-1,3-propanediamine; 2-(2,6-diiodophenyl)-1,3-propanediamine; 2-(2-methoxyphenyl)-1,3-propanediamine; 2-(3-methoxyphenyl)-1,3-propanediamine; 2-(4-methoxyphenyl)-1,3-propanediamine; ; 2-(2-ethoxyphenyl)-1,3-propanediamine; 2-(3-ethoxyphenyl)-1,3-propanediamine; 2-(4-ethoxyphenyl)-1,3-propanediamine; 2-(2-propoxyphenyl)-1,3-propanediamine; 2-(3-propoxyphenyl)-1,3-propanediamine; 2-(4-propoxyphenyl)-1,3-propanediamine; 2-(4-butoxyphenyl)-1,3-propanediamine; 2- (2-benzyloxyphenyl) -1, 3-propanediamine; 2- (3-benzyloxyphenyl)-1, 3-propanediamine; 2- (4-benzyloxyphenyl) -1, 3-propanediamine; 2-(2-methylphenyl)-l,3-propanediamine; 2-(3-methylphenyl)-l,3-propanediamine; 2-(4-methylphenyl)-l,3-propanediamine; 2-(2-ethylphenyl)-l,3-propanediamine; 2-(3-ethylphenyl)-1,3-propanediamine; 2-(4-ethylphenyl)-l,3-propanediamine; 2-(2-isopropylphenyl)-1,3-propanediamine; 2- (3-isopropylphenyl)-l,3-propanediamine; ; 2-(4-isopropylphenyl)-1,3-propanediamine, bp 103-1080C/0.01mm (diHCl salt, mp 284-2870C); 2-(2-trifluoromethylphenyl)-1,3-propanediamine; 2- (3-trifluoromethylphenyl) -1,3-propanediamine; 2-(4-trifluoromethylphenyl)-1,3-propanediamine; 2-(2-methylthiophenyl)-1,3-propanediamine; 2- (4-methylthiophenyl) -1,3-propanediamine; 2- (2-ethylthiophenyl) -1,3-propanediamine; 2- (4-ethylthiophenyl)-l,3-propanediamine; 2-(2-butylthiophenyl)-1,3-propanediamine; 2- (3-butylthiophenyl)-l,3-propanediamine; 2-(4-methsulfinylphenyl)-1,3-propanediamine; 2- (4-ethylsulfonylphenyl) -1,3-propanediamine; 2-(2,4-dimethoxyphenyl)-1,3-propanediamine; 2-(2,6-diethoxyphenyl)-1,3-propanediamine; 2- (3,4-dibenzyloxyphenyl)-1,3-propanediamine; ; 2-(3,5-diethylthiophenyl)-1,3-propanediamine; 2-(2,6-dimethylsulfinylphenyl)-1,3-propanediamine; 2-(2,6-dimethylsulfonylphenyl)-1,3-propanediamine; and the like. PREPARATION D: N-Methyl-2-phenyl-l,3-propane diamines (Reaction Sequence 2) 1. Four and four-tenths (4.4)g of the ethyleneglycol acetal of atropaldehyde is hydrolysed by reaction with 40ml of water and 250mg of oxalic acid in 200ml of ethanol at 700 for about 1 hour. One and four-tenths (1.4)g of N-methylhydrazine is added and the resulting mixture is allowed to stand for 4 hours at room temperature. The mixture is then concentrated to about 50ml, aqueous sodium bicarbonate is added and the mixture is extracted with methylenechloride. The extract is concentrated and distilled, to give 2.2g of 4,5-dihydro1-methyl-4-phenyl-[1H]-pyrrazole, bp 66-72 /0.03mm; ms 160 (M+). A mixture of 3.8 g of 4,5-dihydro-l-methyl-4- phenyl-[lHl-pyrrazole, 50ml of glacial acetic acid, 10ml of 10g hydrochloric acid and lg of a catalyst consisting of 5% platinum on charcoal is stirred under a hydrogen atomosphere for about 6 hours until the calculated amount of hydrogen has been consumed. The mixture is filtered and the filtrate is concentrated under vacuum. The residue is treated with isopropanol and toluene and is concentrated again to remove as much of the water as possible. The residue is refluxed with ether for 3 hours until a powdery solid forms which is collected by filtration. Recrystallization from ethanol gives N-methyl-2-phenyl-l,3-propanediamine hydrochloride, mp 264-2670C. 2. In a similar manner by substituting other ethylene glycol acetals of appropriately phenyl-ring substituted atropaldehydes, other N-methyl-2-substituted phenyl-1,3-propanediamines are prepared such as N-methyl-2- (2-fluorophenyl) -1,3-propanediamine; N-methyl-2-(3-fluorophenyl)-1,3-propanediamine; N-methyl-2- (4-fluorophenyl) -1, 3-propanediamine; N-methyl-2- (2-chlorophenyl) -1, 3-propanediamine; N-methyl-2-l3-chlorophenyl)-1,3-propanediamine; N-methyl-2- (4-chlorophenyl) -1, 3-propanediamine; N-methyl-2-(2-bromophenyl)-1,3-propanediamine; N-methyl-2- (3-bromophenyl) -1, 3-propanediamine; N-methyl-2- (4-bromophenyl) -1, 3-propanediamine; N-methyl-2- (2-iodophenyl) -1, 3-propanediamine; N-methyl-2-(3-iodophenyl)-1,3-propanediamine; ; N-methyl-2- (4-iodophenyl) -1, 3-propanediamine; N-methyl-2-(2,4-dichlorophenyl)-1,3-propanediamine; N-methyl-2-(3,4-dichlorophenyl)-1,3-propanediamine; N-methyl-2-(3,5-dichlorophenyl)-1,3-propanediamine; N-methyl-2-(2,5-dichlorophenyl)-1,3-propanediamine; N-methyl-2-(2,6-dichlorophenyl)-1,3-propanediamine; N-methyl-2-(2,3-difluorophenyl)-1,3-propanediamine; N-methyl-2-(2,4-difluorophenyl)-1,3-propanediamine; N-methyl-2-(3,4-difluorophenyl)-1,3-propanediamine; N-methyl-2-(2,5-difluorophenyl)-1,3-propanediamine; N-methyl-2-(2,6-difluorophenyl)-1,3-propanediamine; N-methyl-2-(3,5-difluorophenyl)-1,3-propanediamine; N-methyl-2-(3,6-dibromophenyl)-1,3-propanediamine; N-methyl-2-(2,4-dibromophenyl)-1,3-propanediamine; N-methyl-2-(3,5-dibromophenyl)-1,3-propanediamine; N-methyl-2-(2,4-diiodophenyl)-1,3-propanediamine; ; N-methyl-2- (2,6-diiodophenyl) -1,3-propanediamine; N-methyl-2-(2-hydroxyphenyl)-1,3-propanediamine; N-methyl-2-(2-methoxyphenyl)-1,3-propanediamine; N-methyl-2-(3-methoxyphenyl)-1,3-propanediamine; N-methyl-2-(4-nethoxyphenyl)-1,3-propanediamine; N-methyl-2- (2-ethoxyphenyl) -1, 3-propanediamine; N-methyl-2- (3-ethoxyphenyl) -1,3-propanediamine; N-methyl-2- (4-ethoxyphenyl) -1,3-propanediamine; N-methyl-2-(2-propoxyphenyl)-1,3-propanediamine; N-methyl-2-(3-propoxyphenyl)-1,3-propanediamine; N-methyl-2- (4-propoxyphenyl) -1,3-propanediamine; N-methyl-2-(3-isopropoxyphenyl)-1,3-propanediamine; N-metbyl-2- (4-butoxyphenyl) -1, 3-propanediamine; N-methyl-2-(2-benzyloxyphenyl)-1,3-propanediamine; N-methyl-2-(3-benzyloxyphenyl)-1,3-propanediamine; ; N-methyl-2-(4-benzyloxyphenyl)-l,3-propanediamine; N-methyl-2- (2-methylphenyl) -1, 3-propanediamine; N-methyl-2- (3-methylphenyl)-1,3-propanediamine; N-methyl-2-(4-methylphenyl)-1,3-propanediamine; N-methyl-2-(2-ethylphenyl)-1,3-propanediamine; N-methyl-2- (3-ethyiphenyl) -1, 3-propanediamine; N-methyl-2- (4-ethylphenyl) -1,3-propanediamine; N-methyl-2- (3-propylphenyl) -1, 3-propanediamine; N-methyl-2- (2-isopropylphenyl)-1,3-propanediamine; N-methyl-2-(3-isopropylphenyl)-1,3-propanediamine; N-methyl-2-(4-isopropylphenyl)-1,3-propanediamine; N-methyl-2- (4-butylphenyl) -1,3-propanediamine; N-methyl-2-(2-trifluoromethylphenyl)-1,3-propane- diamine; N-methyl-2- (3-trifluoromethylphenyl) -1,3-propane- diamine; ; N-methyl-2- (4-tr ifluoromethylphenyl) -1,3-propane- diamine; N-methyl-2-(2-methylthiophenyl)-1,3-propanediamine; N-methyl-2-(4-methylthiophenyl)-1,3-propanediamine; N-methyl-2-(2-ethylthiophenyl)-1,3-propanediamine; N-methyl-2-(4-ethylthiophenyl)-1,3-propanediamine; N-methyl-2-(2-butylthiophenyl)-1,3-propanediamine; N-methyl-2-(3-butylthiophenyl)-1,3-propanediamine; N-methyl-2-(4-methylsulfinylphenyl)-1,3-propanedi- amine; N-methyl-2- (4-ethylsulfonylphenyl) -1, 3-propanedi- amine; N-methyl-2-(2,4-dimethoxyphenyl)-1,3-propanediamine; N-methyl-2-(2,6-diethoxyphenyl)-1,3-propanediamine; N-methyl-2-(3,4-dibenzyloxyphenyl)-1,3-propanedi- amine; N-methyl-2-(3,5-diethylthiophenyl)-1,3-propanedi- amine; N-methyl-2-(2,6-dimethylsulfinylphenyl)-1,3-propane- diamine; ; N-methyl-2- (2,6-dimethylsulfonylphenyl) -1,3-propane- diamine; and the like. 3. By following in principle the procedure of Parts A and B of this Preparation but substituting other N-alkylhydrazines such as N-ethylhydrazine, N-propylhydrazine or N-butylhydrazine for N-methylhydrazine, other diamines are obtained such as N-ethyl-2-phenyl-1,3-propanediamine; N-propyl-2-phenyl-l, 3-propanediamine; N-butyl-2-phenyl-1,3-propanediamine; and the like. PREPARATION E: 2-Phenylglutaramides (Reaction Sequence 3) 1. Twenty-five g of 4-fluorobenzylcyanide is mixed with approximately 3.5ml of freshly distilled acrylonitrile in a suitable reaction vessel. To this stirred mixture is added dropwise a solution of 80mg of sodium methoxide in lml of methanol. When about half of the sodium methoxide is added, there is an exothermic reaction. After all the sodium methoxide is added, the mixture is kept on a steam-bath for 2 hours and is then dissolved in toluene and washed with water. The toluene is removed by evaporation and the residue is separated into its components by fractional distillation to give 18 g of 4-fluorobenzylcyanide, and 2 g of 2-(4-fluorophenyl)glutaronitrile, bp 118-1220C at 0.03 mm. A reaction mixture consisting of 3.Sg of 2-(4-fluorophenyl/glutaronitrile, 25 ml of concentrated sulfuric acid and lml of water is allowed to stand at room temperature over night. The solution is poured into 300 g of ice and is then neutralized with ammonium hydroxide. The product is extracted out with chloroform in a continuous extractor. After three days the product that has formed as a crystalline material in the chloroform is collected to yield 3.01 g of 2-(4-fluorophenyl)-glutaramide, m.p. 154-1570C. 2. Similarly, by following in principle the procedure of Part 3 of this preparation, but substituing other benzylcyanides for 4-fluorobenzylcyanide, other 2-phenylglutaramides are prepared, such as 2-phenylglutaroamide; 2-(2-chlorophenyl)glutaramide; 2-(3-chlorophenyl)glutaramide; 2- (4-chlorophenyl) glutaramide; 2-(2-fluorophenyl)glutaramide; 2-(3-fluorophenyl)glutaramide; 2-(2-bromophenyl)glutaramide; 2-(3-bromophenyl)glutaramide; 2-(4-bromophenyl)glutaramide; 2-(2-iodophenyl)glutaramide; 2-(3-iodophenyl)glutaramide; 2-(4-iodophenyl)glutaramide; 2- (2, 3-dichlorophenyl) glutaramide; 2- (2, 4-dichlorophenyl) glutaramide; 2-(3,4-dichlorophenyl)glutaramide; 2- (3,5-dichlorophenyl) glutaramide; 2- (2,5-dichlorophenyl) glutaramide; 2- (2,3-difluorophenyl) glutaramide; 2- (2, 4-difluorophenyl) glutaramide; ; 2-(3,4-difluorophenyl)glutaramide; 2-(2,5-difluorophenyl)glutaramide; 2-(2,6-difluorophenyl)glutaramide; 2-(3,5-difluorophenyl)glutaramide; 2-(2,6-dibromophenyl)glutaramide; 2-(2,4-dibromophenyl)glutaramide; 2-(3,5-dibromophenyl)glutaramide; 2-(2,4-diiodophenyl)glutaramide; 2-(2,6-diiodophenyl)glutaramide; 2- (3-methoxyphenyl) glutaramide; 2- (2-methoxyphenyl) glutaramide; 2-(4-methoxyphenyl)glutaramide; 2-(2-ethoxyphenyl)glutaramide; 2-(3-ethoxyphenyl)glutaramide; 2-(4-ethoxyphenyl)glutaramide; 2-(2-propoxyphenyl)glutaramide; 2-(3-propoxyphenyl)glutaramide; 2-(4-propoxyphenyl)glutaramide; 2-(4-butoxyphenyl)glutaramide; 2-(2-benzyloxyphenyl)glutaramide; 2- (3-benzyloxyphenyl) glutaramide; 2-(4-benzyloxyphenyl)glutaramide; 2-(2-methylphenyl)glutaramide; 2- (3-methylphenyl) glutaramide; 2-(4-methylphenyl)glutaramide; 2-(2-ethylphenyl)glutaramide; 2-(3-ethylphenyl)glutaramide; 2-(4-ethylphenyl)glutaramide; 2-(2-isopropylphenyl)glutaramide; 2-(3-isopropylphenyl)glutaronitrole; 2-(4-isopropylphenyl)glutaramide; 2-(2-trifluoromethylphenyl)glutaramide; 2-(3-trifluoromethylphenyl)glutaramide; 2-(4-trifluoromethylphenyl)glutaramide; 2- (2-methylthiophenyl) glutaramide; 2-(4-methylthiophenyl)glutaramide; 2-(2-ethylthiophenyl)glutaramide; 2-(4-ethylthiophenyl)glutaramide; 2-(2-butylthiophenyl)glutaramide; 2-(3-butylthiophenyl)glutaramide; 2-(4-methsulfinylphenyl)glutaramide; 2-(4-ethylsulfonylphenyl)glutaramide; 2-(2,4-dimethoxyphenyl)glutaramide; 2- (2,6-diethoxyphenyl)glutaramide; 2-(3,5-diethylthiophenyl)glutaramide; 2- (2,6-dimethylsulfinylphenyl) glutaramide; 2- (2,6-dimethylsulfonylphenyl)glutaramide; and the like. PREPARATION F: l-phenyl-l, 3-propanediamines (Reaction Sequence 3) A. l-Phenyl-1,3-propanediamine. A solution of 27g of potassium hydroxide in 150ml of water is cooled to -20C and 17g of bromine is added in a thin stream. The mixture is stirred for 10 min. and 10g of 2-phenylglutaramide is then added. Stirring is continued while the temperature is kept at -30 to +20C until there is a clear solution (about 15 min.). The solution is then stirred at room temperature for 30 mins. and finally at 600C for 90 min. It is cooled and extracted several times with methylene chloride and the combined extracts are dried over sodium sulfate, filtered and concentrated. The residue is distilled to yield 4.2g of l-phenyl-1,3-propanediamine, b.p. 84-870C at 0.5mm. When 2.2g of the diamine is dissolved in 25ml of ethanol that contains 1.3g of hydrogen chloride there is crystallization of the dihydrochloride salt which is collected and dried at 800C under vacuum to yield 2.8g of l-phenyl-1,3-propanediamine dihydrochloride, m.p. 244-2460C. B. Other l-phenylpropanediames are prepared by following in principle the procedure of Part A of this procedure substituting other 2-phenylglutaramides of Part 2 of Preparation E for 2-phenylgutaramide in Part A of this procedure. PREPARATION G: B-Amino-2-cinnamonitriles (Reaction Sequence 4) 1. B-Amino-2-trifluoromethylcinnamonitrile. A mixture consisting of 9.3g of 2-trifluoromethylbenzonitrile, 4.5g of acetonitrile, 4.3g of sodium amide and 100ml of ether is stirred and refluxed under nitrogen over night. The resulting solid is collected on a Buchner-funnel, washed with ether and dissolved in approximately 100 ml of cold ethanol. Crushed ice is added to this solution until the total volume is about 700ml. This mixture is allowed to stand for several hours. The resulting solid precipitate is collected by filtration then dissolved in methanol and decolorizing charcoal is added. The charcoal/methanol mixture is filtered and the filtrate is gradually treated with water until crystallization is judged complete. The crystalline solid is collected and dried under vacuum, to give 7.75 g of B-amino-2-trifluoromethylcinnamonitrile, mp 101-103 . 2. Similarly, by following in principle the procedure of Part 1 of this Preparation, but substituting other appropriately substituted benzonitriles for 2-trifluoromethylbenzonitrile, other corresponding B-amino-substituted cinnamonitriles are prepared such as B-aminocinnamonitrile; B-amino-2-fluorocinnamonitrile; B-amino-3-fluorocinnamonitrile; B-amino-4-fluorocinnamonitrile; B-amino-2-chlorocinnamonitrile; B-amino-3-chlorocinnamonitrile; 8-amino-4-chlorocinnamonitrile; B-amino-3-bromocinnamonitrile; B-amino-4-iodocinnamonitrile; B-amino-2-methylcinnamonitrile; B-amino-4-methylcinnamonitrile, mp lll-1130C; B-amino-2-ethylcinnamonitrile; B-amino-4-t-butylcinnamonitrile; B-amino-2-methoxycinnamonitrile; 8-amino-3-methoxycinnamonitrile, mp 74-750C; ; B-amino-3-ethoxycinnamonitrile; B-amino-4-isopropoxycinnamonitrile; B-amino-2-methylthiocinnamonitrile; 8-amino-4-isobutylthiocinnamonitrile; (3-amino-4-methylsulfinylcinnamoni tr ile; 8-amino-4-methylsulfonylcinnamonitrile; 8-amino-2,4-difluorocinnamonitrile; B-amino-2,6-dichlorocinnamonitrile; B-amino-2,6-dibromocinnamonitrile; B-amino-2,4-diiodocinnamonitrile; ss-amino-2,4-dimethylcinnamonitrile; B-amino-2,6-disopropylcinnamonitrile; B-amino-2,4-dimethoxycinnamonitrile; B-amino-2,6-diethoxycinnamonitrile; 8-amino-2,4-dimethylthiocinnamonitrile; 6-amino-2,6-dimethylsulfinylcinnamonitrile; and the like. PREPARATION H: l-phenyl-1,3-propanediamines (Reaction Sequence 4) 1. 1- (2-Trifluoromethylphenyl) -1, 3-propanediamine. Sixty (60)ml of 1 molar borane in tetrahydrofuran is added to a solution of 7.6g of 8-amino-2-trifluoromethyl- cinnamonitrile (prepared according to Preparation D, Part 1) in 100 ml of ether. The mixture is stirred at room temperature overnight, then treated with 10ml of water, and stirred for 45 minutes. The resulting mixture is concentrated under reduced pressure and 200ml of isopropanol and 80ml of 20% hydrochloric acid are added thereto. This mixture is refluxed for 2 hours, then concentrated to a small volume. The residue is made alkaline by addition of excess of 20% sodium hydroxide and is extracted 3 times with methylene chloride. The extracts are combined, concentrated and distilled to give 1.7 g of 1-(2-trifluoromethylphenyl)-1,3-propanediamine, bp 73-77 C/0.1mm. The hydrochloric salt is obtained by dissolving the diamine in ethanolic hydrogen chloride and adding ether to this solution to give the diHCl salt of l-(2-tri fluoromethylphenyl)-1,3-propanediamine, mp 213-127 . 2. Similarly, by following in principle the process of Part 1 of this preparation but substituting a suitable S-aminocinnamonitrile (prepared according to Preparation D, Part 2) for B-amino-2-trifluoromethyl- cinnamonitrile, other corresponding propanediamines are prepared such as l-phenyl-1,3-propanediamine, bp 84-870C/0.5 mm (diHCl salt, mp 244-2460C); 1- (2-fluorophenyl) -1, 3-propanediamine; 1-(3-fluorophenyl)-1,3-propanediamine; 1-(4-fluorophenyl)-1,3-propanediamine, bp 84-880C/0.7 mm (diHCl salt 262-2660C); 1- (2-chlorophenyl) -1, 2-propanediamine; 1- (3-chlorophenyl) -1, 2-propanediamine; 1-(4-chlorophenyl)-1,2-propanediamine; 1-(3-bromophenyl)-1,2-propanediamine; 1-(4-iodophenyl)-1,2-propanediamine; ; 1- (2-methylphenyl) -1, 2-propanediamine; 1-(4-methylphenyl)-1,2-propanediamine; 1-(2-ethylphenyl)-1,2-propanediamine; 1-(4-t-butylphenyl)-1,2-propanediamine; 1- (2-methoxyphenyl) -1,2-propanediamine; 1-(3-methoxyphenyl)-1,2-propanediamine, b.p. 1201260C at 1 mm (diHCl salt, m.p. 225-2270C.); 1-(3-ethoxyphenyl)-1,2-propanediamine; 1- (4-isopropoxyphenyl)-1,2-propanediamine; 1-(2-methylthiophenyl)-1,2-propanediamine; 1- (4-isobutylthiophenyl) -1,2-propanediamine; 1-(4-methylsulfinylphenyl)-1,2-propanediamine; 1-(4-methylsulfonylphenyl)-1,2-propanediamine; 1- (2,4-difluorophenyl)-l, 2-propanediamine; 1- (2, 6-dichlorophenyl) -1, 2-propanediamine; 1- (2, 6-dibromophenyl) -1, 2-propanediamine; ; 1- (2, 4-diiodophenyl) -1, 2-propanediamine; 1-(2,4-dimethylphenyl)-1,2-propanediamine; 1- (2,6-disopropylphenyl) -1, 2-propanediamine; 1- (2, 4-dimethoxyphenyl) -1, 2-propanediamine; 1-(2,6-diethoxyphenyl)-1,2-propanediamine; 1-(2,4-dimethylthiophenyl)-1,2-propanediamine; l-(2,6-dimethylsulfinyl; and the like. EXAMPLE 1: 2-Amino-5-phenyl-1,4,5,6- tetrahydropyr imidines. A. A solution of 1.55 g of 2-(3-bromophenyl)1,3-propanediamine (prepared in accordance with Preparation C, Part 2) and 0.72 g of cyanogenbromide in 300 ml of methanol is maintained at room temperature for three days and is then refluxed for 6 hours. The solvent is evaporated off by a rotary evaporator. The residue is dissolved in boiling isopropanol which then is filtered through a steam-jacketed funnel. The crystals which form as the filtrate are cooled is collected by filtration and dried under vacuum to give 0.87g of the hydrobromide salt of 2-amino-5-(3-bromophenyl)-1,4,5,6-tetrahydropyrimidine, mp 223-2270C. B. A stirred mixture consisting of 3.25g of 2-phenyl-l,3-propanediamine (prepared in accordance with Preparation C) and 3.02g of 2-methyl-2-thiopseudourea sulfate ([CH3SC(NH)NH2]2H2S04) in a small flask is immersed in a 2450C oil bath. The temperature is raised to 2650C when the reaction mixture solidifies. When the reaction mixture melts again, it is stirred for about five minutes then is removed from the oil-bath. The contents are refluxed with 50 ml of methanol until a powder is formed. The mixture is cooled and the solid product is collected on a Buchner-funnel, washed with 30% ether in methanol and is air-dried to give 3.7g of crude product. Recrystallization from 20ml of water yields 2.25g of 2-amino-5-phenyl-1,4,5,6-tetrahydropyrim sulfate, mp 264-2670C. C. By following in principle the procedures of Parts A or B of this example but substituting other appropriate 2-(substituted phenyl)-l,3-propanediamines prepared according to Preparation C for 2-(3-bromo phenyl) -1,3-propanediamine and 2-phenyl-1,3-propanediamine other compounds of this invention are prepared such as 2-amino-5-(2-chlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(3-chlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(4-chlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2-fluorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(3-fluorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-S- (4-fluorophenyl) -1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2-bromophenyl)-1,4,5,6-tetrahydro- pyrimidine; ; 2-amino-5-(4-bromophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2-iodophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(3-iodophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(4-iodophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2,4-dichlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(3,5-dichlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2,5-dichlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2,6-dichlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2,3-difluorophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-5-(2,4-difluorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2,5-difluorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2,6-difluorophenyl)-1,4,5,6-tetrahydro- pyrimidine; ; 2-amino-5-(3,5-difluorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(3,6-dibromophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-5-(2,4-dibromophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(3,5-dibromophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-5-(2,4-diiodophenyl)-1,4,5,6-tetrahydro pyr imidine; 2-amino-5-(2,6-diiodophenyl)-1,4,5,6-tetrahydro pyr imidine; 2-amino-5-(2-trifluoromethylphenyl)-1,4,5,6-tetra- hydropyr imidine; 2-amino-5-(2-methoxyphenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-5-(4-methoxyphenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-5-(2-ethoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(3-ethoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; ; 2-amino-5-(4-ethoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2-propoxyphenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-5-(3-propoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(4-propoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(4-butoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(4-methylphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2-methylphenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-5-(3-methylphenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-5-(3-ethylphenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-5-(4-ethylphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2-ethylphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2-isopropylphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(3-isopropylphenyl)-1,4,5,6-tetrahydro- pyr imidine; ; 2-amino-5-(4-isopropylphenyl)-1,4,5,6-tetrahydro pyr imidine; 2-amino-5-(2-trifluoromethylphenyl)-1,4,5,6-tetra- hydropyr imidine 2-amino-5-(3-trifluoromethylphenyl)-1,4,5,6-tetra- hydropyr imidine; 2-amino-5-(4-trifluoromethylphenyl)-1,4,5,6-tetra- hydropyr imidine; 2-amino-5-(2-methylthiophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-5-(4-methylthiophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2-ethylthiophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-5-(4-ethylthiophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2-butylthiophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(3-butylthiophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(4-methsulfinylphenyl)-1,4,5,6-tetrahydro- pyr imidine; ; 2-amino-5-(4-ethylsulfonylphenyl)-1,4,5,6-tetra- hydropyr imidine; 2-amino-5-(2,4-dimethoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(2,6-diethoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-5-(3,5-diethylthiophenyl)-1,4,5,6-tetra hydropyr imidine; 2-amino-5-(2,6-dimethylsulfinylphenyl)-1,4,5,6 tetrahydropyr imidine; 2-amino-5-(2,6-dimethylsulfonylphenyl)-1,4,5,6- tetrahydropyrimidine; and the like. EXAMPLE 2: l-Alkyl 2-amino-5-phenyl-1,4,5,6 tetrahydropyr imidines. A. l-methyl-2-amino-S-phenyl-l,4 ,S ,6-tetrahydro- pyrimidine A slurry of 0.55 g of the dihydrochloride salt of N-methyl-2-phenyl-1,3-propanediamine in 25 ml of ethanol is stirred with 0.3 g of sodium methoxide for 30 min. The precipitated sodium chloride is removed by filtration and the filtrate is concentrated. The residue is mixed with 0.322 g of 2-methyl-2-thiopseudourea sulfate and the mixture is stirred in a 2400C oil-bath for 10 min. The crude reaction product is then refluxed with isopropanol for 2 hours, cooled and the solid is collected and recrystallized from 6-7ml of water to give 0.2g of the sulfate salt of l-methyl-2-amino-5-phenyl-1,4.5,6- tetrahydropyrimidine, m.p. 254-2570C. B. In a similar manner, by following in principle the procedure of Part A of this example but substituting other N-methyl-2-phenyl-l, 3-propanediamines prepared in accordance with Preparation D, Part 2 for N-methyl-2-phenyl-l,3-propanediamine other compounds of this invention are prepared such as l-methyl-2-amino-5- (2-chlorophenyl) -1,4,5,6-tetra- hydro-pyrimidine; l-methyl-2-amino-5- (3-chlorophenyl)-l,4,5,6-tetra- hydro-pyrimidine; l-methyl-2-amino-5-(4-chlorophenyl)-1,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5- (2-fluorophenyl)-l,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(3-fluorophenyl)-l,4,5,6-tetra- hydropyrimidine; l-methyl-2-amino-5-(4-fluorophenyl)-1,4,5,6-tetra hydropyr imidine; ; 1-methyl-2-amino-5-(2-bromophenyl)-1,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(4-bromophenyl)-1,4,5,6-tetra hydropyr imidine; 1-methyl-2-amino-5-(2-iodophenyl)-1,4,5,6-tetra- hydropyrimidine; 1-methyl-2-amino-5-(3-iodophenyl)-1,4,5,6-tetra- hydropyrimidine; 1-methyl-2-amino-5-(4-iodophenyl)-1,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(2,4-dichlorophenyl)-1,4,5,6- tetrahydropyr imidine; 1-methyl-2-amino-5-(3,5-dichlorophenyl)-1,4,5,6- tetrahydropyr imidine; 1-methyl-2-amino-5-(2,5-di-chlorophenyl)-1,4,5,6- tetr ahydropyr imidine; l-methyl-2-amino-5-(2,6-dichlorophenyl)-1,4,5,6- tetrahydropyr imidine; l-methyl-2-amino-5-(2,3-difluorophenyl)-1,4,5,6- tetrahydropyrimidine; ; 1-methyl-2-amino-5-(2,4-difluorophenyl)-l,4,5,6 tetrahydropyr imidine; l-methyl-2-amino-5-(2,5-difluorophenyl)-1,4,5,6- tetrahydropyrimidine; 1-methyl-2-amino-5-(2,6-difluorophenyl)-1,4,5,6- tetrahydropyr imidine; 1-methyl-2-amino-5-(3,5-difluorophenyl)-1,4,5,6- tetrahydropyrimidine; l-methyl-2-amino-5-(3,6-dibromophenyl)-1,4,5,6- tetrahydropyrimidine; l-methyl-2-amino-5-(2,4-dibromophenyl)-1,4,5,6- tetr ahydropyr imidine; 1-methyl-2-amino-5-(3,5-dibromophenyl)-1,4,5,6- tetrahydropyrimidine; 1-methyl-2-amino-5-(2,4-diiodophenyl)-1,4,5,6- tetrahydropyr imidine; l-methyl-2-amino-S-(2,6-diiodophenyl)-1,4,5,6- tetrahydropyr imidine; 1-methyl-2-amino-5-(2-trifluoromethylphenyl)-1,4,5,6-t etrahydropyr imidine; ; l-methyl-2-amino-S- (2-methoxyphenyl) -1,4,5,6- tetrahydropyr imidine; 1-methyl-2-amino-5-(4-methoxyphenyl)-1,4,5,6-tetra- hydro-pyrimidine; l-methyl-2-amino-5- (2-ethoxyphenyl)-l,4,5,6-tetra hydroyrimidine; 1-methyl-2-amino-5-(3-ethoxyphenyl)-1,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(4-ethoxyphenyl)-1,4,5,6-tetra hydropyr imidine; l-methyl-2-amino-5-(2-propoxyphenyl)-1,4,5,6-tetra- hydropyr imidine; 1-methyl-2-amino-5-(3-propoxyphenyl)-1,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(4-propoxyphenyl)-1,4,.5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(4-butoxyphenyl)-1,4,5,6-tetra hydropyr imidine; l-methyl-2-amino-5-(4-methylphenyl)-1,4,5,6-tetra- hydropyr imidine; ; 1-methyl-2-amino-5-(2-methylphenyl)-1,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(3-methylphenyl)-1,4,5,6-tetra- hydropyrimidine; l-methyl-2-amino-5- (3-ethylphenyl)-l,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(4-ethylphenyl)-1,4,5,6-tetra hydropyr imidine; l-methyl-2-a.mino-5-(2-ethylphenyl)-1,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(2-isopropylphenyl)-1,4,5,6-tetra hydropyr imidine; l-methyl-2-amino-5-(3-isopropylphenyl)-1,4,5,6-tetra- hydropyr imidine; 1-methyl-2-amino-5-(4-isopropylphenyl)-1,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(2-trifluoromethylphenyl)-1,4,5,6- tetrahydropyrimidine - l-methyl-2-amino-5-(3-trifluoromethylphenyl)-1,4,5,6- tetrahydropyr imidine; ; l-methyl-2-amino-5-(4-trifluoromethylphenyl)-1,4,5,6- tetrahydropyr imidine; l-methyl-2-amino-S- (2-methylthiophenyl)-1, 4,5,6- tetrahydropyr imidine; l-methyl-2-amino-S- (4-methylthiophenyl) -1,4,5,6- tetrahydropyr imidine; 1-methyl-2-amino-5-(2-ethylthiophenyl)-1,4,5,6-tetra- hydropyr imidine; 1-methyl-2-amino-5-(4-ethylthiophenyl)-1,4,5,6-tetra- hydropyrimidine; 1-methyl-2-amino-5-(2-butylthiophenyl)-1,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(3-butylthiophenyl)-1,4,5,6-tetra- hydropyr imidine; l-methyl-2-amino-5-(4-methsulfinylphenyl)-1,4,5,6- tetrahydropyr imidine; 1-methyl-2-amino-5-(4-ethylsulfonylphenyl)-1,4,5,6- tetrahydropyr imidine; l-methyl-2-amino-5- (2,4-dimethoxyphenyl)-l,4,S,6- tetrahydropyr imidine; ; 1-methyl-2-amino-5-(2,6-diethoxyphenyl)-1,4,5,6- tetrahydropyr imidine; l-methyl-2-amino-5- (3, 5-diethylthiophenyl) -1,4,5,6- tetrahydropyrimidine; l-methyl-2-amino-5- (2,6-dimethylsulfinylphenyl) - 1,4,5,6-tetrahydropyrimidine; l-methyl-2-amino-5- (2, 6-dimethylsulfonylphenyl) - 1,4,5,6-tetrahydropyrimidine; and the like. C. In a similar manner, by following in principle the procedure of Part A of this example but substituting other N-alkyl-2-phenyl-1,3-propanediamines prepared in accordance with Preparation D, Part 3 for N-methyl-2phenyl-1,3-propanediamine other compounds of this invention are prepared such as l-ethyl-2-amino-5-phenyl-1,4,5,6-tetrahydro- pyr imidine; l-propyl-2-amino-5-phenyl-1,4,5,6-tetrahydro- pyr imidine; l-butyl-2-amino-5-phenyl-l,4,5 , 6-tetrahydro- pyrimidine; and other N-alkyl homologs of the compounds of Part B of this Example. EXAMPLE 3: 2-Alkylcarbonylamino-5-phenyl 1,4,5 ,6-tetrahydropyrimidines. A. Acetamido-5-phenyl-l,4,5,6-tetrahydropyrimidine A slurry of 600mg (2.67mmole) of the sulfate salt of 2-amino-5-phenyl-1,4,5,6-tetrahydropyrimidine (prepared in accordance with Example 1) in 50ml of ethanol and 145mg (2.67mmole) of sodium methoxide are stirred for 2 hours. The mixture is filtered to remove the insoluble sodium chloride and the solvent is removed under vacuum. The oil residue is dissolved in 100 ml of methylene chloride, 415mg (1.33mmole) of N,N',N'',N " '-tetra- acetylglycoluril is added and the resulting solutions is stirred at room temperature overnight. A precipitate that has formed is removed by filtration and the filtrate is concentrated. The residue is treated with approximately 25ml of an acetonitrile-ethyl=acetate mixture and the insoluble product is collected by filtration to yield 320mg of a product having a m.p. 241-2450C. Upon purification by recrystallization from methanol, 2-acetamido-5phenyl-1,4,5,6-tetrahydropyrimidine is obtained, m.p. 246-249 0C. B. Similarly, by following the procedure of Part A of this example -but substituting tetrapropionylglycoluril or tetrabutyrylglycoluril for tetracetylglycoluril other amides of this invention are prepared such as 2-propionamido-5-phenyl-1,4,5,6-tetrahydropyrimidine or 2-butyramido-5-phenyl-1,4,5,6-tetrahydropyrimidine. C. Similarly, by following the procedures of Parts A and B of this example, but substituting the other 2-amino-5-phenyl-1,4,5,6-tetrahydropyrimidine of Example 1, Part C.for 2-amino-5-phenyl-1,4,5,6-tetrahydropyrimide, the corresponding 2-acetamido, 2-propionamido or 2-butyramido-5-phenyl-1,4,5,6-tetrahydropyrimidines are prepared. EXAMPLE 4: l-Alkyl 2-alkylcarbonylamino-4-phenyl 1,4,5 ,6-tetrahydropyrimidines. A. By following in principle the procedure of Example 3, Parts A and B but substituting l-methyl-2-amino-5-phenyl-1,4,5,6-tetrahydropyrimidine for 2-amino-S-phenyl-l,4 ,5 ,6-tetrahydropyrimidine other compounds of this invention are prepared such as l-methyl-2-acetamido-5-phenyl-1,4,5,6-tetrahydro- pyr imidine; l-methyl-2-propionami o-5-phenyzl-1,4,5,6-tetrahydro- pyr imidine; l-methyl-2-butyramido-5-phenyl-1, 4,5, 6-tetrahydro- pyrimidine; and the like. B. Similarly, by following the procedures of Part A of this example, but substituting the other l-alkyl-2 amino-5-phenyl-1,4,5,6-tetrahydropyrimidine of Example 2, Part C for l-methyl-2-amino-S-phenyl-1,4,5,6-tetra- hydropyrimide, the corresponding 1-alkyl-2-acetamido, 2-propionamido or 2-butyramido-S-phenyl-l, 4,5, 6-tetr a- hydropyrimidines are prepared which correspond to the 2-amines of Example 2, Part C. EXAMPLE 5: 2-Alkoxycarbonylamino-5-phenyl1,4,5 ,6-tetrahydropyrimidines A. 2-Methoxycarbonylamino-5- (3-methoxyphenyl) - 1,4,5 ,6-tetrahydropyrimidine. A solution of 2.61 g (14.5 m. mole) of 2-(3-methoxyphenyl)-1,3-propanediamine in 200 ml of methanol is combined with a solution of 3.0 g (14.55 m. mole) of 1,3-bis(methoxycarbonyl)-S-methylisothiourea in 200 ml of methanol and allowed to stand at room temperature over night. The crystalline product which separates is collected, washed with methanol and dried at 780 under vacuum to give 2.62 g of 2-methoxycarbonylamino-5 (3-methoxyphenyl)-1,4,5,6-tetrahydropyrimidine, mp 218-2210. B. Similarly, by following in principle the process of Part A of this example but substituting other 2- (optionally substituted phenyl)-1,3-propanediamines prepared according to the process of Preparation C, Part 2 for 2-(3-methoxyphenyl)-1,3-propanediamine), other compounds of this invention are prepared such as 2-methoxycarbonylamino-5-phenyl-1,4,5,6-tetra- hydropyrimidine, m.p. 333-3360C; 2-methoxyzarbonylamino-5-(2-chlorophenyl)-1,4,5,6- tetrahydropyrimidine, mp 353-3570C; 2-methoxycarbonylamino-5-(3-chlorophenyl)-1,4,5,6 tetrahydropyr imidine; 2-methoxyzarbonylamino-5-(4-chlorophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-5-(2-fluorophenyl)-1,4,5,6- tetrahydropyrimidine; ; 2-methoxycarbonylamino-5-(3-fluorophenyl)-1,4,5,6- tetrahydropyrimidine; 2-methoxycarbonylamino-5-(4-fluorophenyl)-1,4,5,6- tetrahydropyrimidine, mp 225-2350C (decomposes) mp HC1 salt 179-1820C; 2-methoxyearbonylamino-5-(2-bromophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-5-(3-bromophenyl)-1,4,5,6- tetrahydropyrimidine, mp 213-2150C; 2-methoxycarbonylamino-5-(4-bromophenyl)-1,4,5,6- tetrahydropyrimidine; 2-methoxycarbonylamino-5-(2-iodophenyl)-1,4,5,6- tetrahydropyrimidine; 2-methoxycarbonylamino-5-(3-iodophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-5-(4-iodophenyl)-1,4,5,6- tetrahydropyr imidine; ; 2-methoxycarbonylamino-5-(2,4-dichlorophenyl)- 1,4,5,6-tetrahydropyrimidine, (C1 salt, mp 209-2100C); 2-methoxycarbonylamino-5- (3, 5-dichlorophenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(2,5-dichlorophenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(2,6-dichlorophenyl)- 1,4,5,6-tetrahydropyrimidine, m.p. 231-2340C; 2-methoxyzarbonylamino-5-(2,3-difluorophenyl)- 1,4,5 ,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(2,4-difluorophenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(2,5-difluorophenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(2,6-difluorophenyl)- 1,4 ,5,6-tetrahydropyrimidine; ; 2-methoxycarbonylamino-5- (3, 5-difluorophenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(3,6-dibromophenyl)-l,4,5,6 tetrahydropyr imidine; 2-methOxycarbonylamino-5-(2,4-dibromophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-5-(3,5-dibromophenyl)-1,4,5,6- tetrahydropyrimidine; 2-methoxycarbonylamino-5-(2,4-diiodophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-5-(2,6-diiodophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-5-(2-methoxyphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-5-(4-methoxyphenyl)-1,4,5,6tetrahydropyrimidine; 2-methoxycarbonylamino-5-(2-ethoxyphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-5-(3-ethoxyphenyl)-1,4,5,6- tetrahydropyr imidine; ; 2-methoxycarbonylamino-5-(4-ethoxyphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-5-(2-propoxyphenyl)-1,4,5,6- tetrahydropyrimidine; 2-methoxycarbonylamino-5-(3-propoxyphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-5-(4-propoxyphenyl)-1,4,5,6tetrahydropyrimidine; 2-methoxycarbonylamino-5-(4-butoxyphenyl)-1,4,5,6- tetr ahydropyr imidine; 2-methoxycarbonylamino-5-(2-methylphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxyzarbonylamino-5-(3-methylphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxyzarbonylamino-5-(4-methylphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-5-(2-ethylphenyl)-1,4,5,6- tetrahydropyr imidine; ; 2-methoxycarbonylamino-5-(3-ethylphenyl)-1,4,5,6- tetr ahydropyr imidine; 2-methoxyzarbonylamino-5-(4-ethylphenyl)-1,4,5,6- tetrahydropyrimidine; 2-methoxycarbonylamino-5-(2-isopropylphenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5- (3-isopropylphenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(4-isopropylphenyl)1,4,5,6-tetrahydropyrimidine, ms 275 (M+); 2-methoxycarbonylamino-5-(2-trifluoromethylphenyl)1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(3-trifluoromethylphenyl)1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-S- (4-trifluoromethylphenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(2-methylthiophenyl)1,4,5,6-tetrahydropyrimidine; 2-methoxyzarbonylamino-5-(4-methylthiophenyl)- 1,4,5,6-tetrahydropyrimidine; ; 2-methoxycarbonylamino-5- (2-ethylthiophenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(4-ethylthiophenyl)1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(2-butylthiophenyl)1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-S- (3-butylthiophenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5-(4-methylsulfinylphenyl)1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-5- (4-ethylsulfonylphenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-S- (2, 4-dimethoxyphenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-(2,6-diethoxyphenyl)-1,4,5,6- tetr ahydropyr imidine; 2-methoxycarbonylamino- (3, 5-diethylthiophenyl)- 1,4,5,6-tetrahydropyrimidine; ; 2-methoxycarbonylamino- (2,6-dimethylsulfinylphenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxyzarbonylamino-(2,6-dimethylsulfonylphenyl)- 1,4,5,6-tetrahydropyrimidine; and the like. C. Similarly, by following in principle the procedures of Part A of this example but substituting other bis-1,3(alkoxycarbonyl)-S-methylisothiourea or mono-lalkoxycarbonyl-S-methylisothiourea such as l-ethoxycarbonyl-S-methylisothiourea or l-butoxycarbonyl-S-l-propoxycarbonyl-S-methylisothiourea for bis-1,3- (methoxy- carbonyl)-S-methylisothiourea and a suitable 2-phenyl-1,3propanediamine for 2- (methoxyphenyl) -1, 3-propanediamine, other 2-alkoxycarbonylamino-5-phenyl-1,4,5,6-tetra- hydropyrimides are prepared such as 2-ethoxyzarbonylamino-5-phenyl-1,4,5,6-tetrahydro- pyrimidine, mp 338-3430C; 2-isopropoxycarbonylamino-5-phenyl-1,4,5,6-tetra- hydropyrimidine, mp 335-342 C, ms 261 (M+); ; 2-n-butoxycarbonylamino-5-phenyl-1,4,5,6-tetrahydro pyr imidine; 2-n-propoxyearbonylamino-5-(3-bromophenyl)-1,4,5,6- tetrahydropyrimidine, mp 205-2060C; 2-i-propoxycarbonylamino-5-(2,6-dichlorophenyl)1,4,5,6-tetrahydropyrimidine, mp 199-2010C; and the like. EXAMPLE 6: l-Alkyl-2-alkoxycarbonylamino-5-phenyl- 1,4,5 ,6-tetrahydropyrimidines A. l-Methyl-2-methoxycarbonylamino-S-phenyl- 1,4,5 ,6-tetrahydropyrimidine To a solution of 1.5 g of the dihydrochloride of N-methyl-2-phenyl-1,3-propane diamine (prepared in accordance with Preparation F, Part A) in 200ml of methanol is added first 0.68g of sodium methoxide in a little methanol and then a solution of 1.3g of 1,3-bis (methoxycarbonyl) -S-methylisothiourea in 200ml of methanol. This mixture is allowed to stand at room temperature of 16 hours, is refluxed for 1 hour and is then concentrated to near dryness. The residue is dissolved in 50ml of 3% hydrochloric acid and the resulting solution is washed with ether to remove non-basis impurities. The product is then precipitated by addition of saturated sodium bicarbonate. The solid is collected, washed with fresh water and dried under vacuum to give 0.999 of product, mp 177-179. Recrystallization from ether gives l-methyl-2-methyoxy carbonylamino-5-phenyl-1,4,5,6-tetrahydropyrimidine, mp 176-1770. B. In a similar manner by substituting other N-methyl-2-phenyl-l, 3-propanediamines (prepared in accordance with Preparation F, Part B) for N-methyl-2phenyl-1,3-propanediamine, other compounds of this invention are prepared such as l-methyl-2-alkoxycarbonylamino-5- (2-fluorophenyl) - 1,4,5,6-tetrahydropyrimidine; 1-methyl-2-alkoxycarbonylamino-5- (3-fluorophenyl) - 1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(4-fluorophenyl)1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(2-chlorophenyl)1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(3-chlorophenyl)1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(4-chlorophenyl)1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(3-bromophenyl)1,4,5,6-tetrahydropyrimidine; ; l-methyl-2-alkoxycarbonylamino-5-(4-iodophenyl)1,4,5,6-tetrahydropyrimidine; 1-methyl-2-alkoxycarbonylamino-5- (2-hydroxyphenyl) - 1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(2-methoxyphenyl)1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5- (3-methoxyphenyl) - 1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(4-methoxyphenyl)1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(2-ethoxyphenyl)1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-S- (3-isopropoxy- phenyl)-1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxyearbonylamino-5-(4-benzyloxyphenyl) phenyl)-1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(4-t-butoxyphenyl)1,4,5,6-tetrahydropyrimidine; ; l-methyl-2-alkoxycarbonylamino-5-(2-methylphenyl) 1,4,5 ,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(3-methylphenyl)1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(4-methylphenyl)1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-S- (2-ethylphenyl) - 1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(3-propylphenyl)1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5- (4-butylphenyl) - 1,4,5 ,6-tetrahydropyrimidine; 1-methyl-2-alkoxyzarbonylamino-5-(2-methylthio- phenyl)-1,4,5,6-tetrahydropyrimidine; 1-methyl-2-alkoxycarbonylamino-5-(3-ethylthio- phenyl) -1,4,5, 6-tetrahydropyr imidine; 1-methyl-2-alkoxycarbonylamino-5-(4-butylthio- phenyl)-1,4,5,6-tetrahydropyrimidine; ; l-methyl-2-alkoxycarbonylamino-S- (4-methylsulfinyl- phenyl) -1,4,5, 6-tetrahydropyr imidine; l-methyl-2-alkoxycarbonylamino-5-(4-ethylsulfinyl phenyl)-1,4,5,6-tetrahydropyrimidine; 1-methyl-2-alkoxyzarbonylamino-5-(2,4-difluoro- phenyl)-1,4,5,6-tetrahydropyrimidine; 1-methyl-2-alkoxycarbonylamino-5-(2,6-dichloro- phenyl)-1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-S- (3,5-dibromo- phenyl)-1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxyearbonylamino-5-(2,4-diiodophenyl)- 1,4,5,6-tetrahydropyrimidine; 1-methyl-2-alkoxycarbonylamino-5-(2,6-dihydroxy- phenyl)-1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxyzarbonylamino-5-(2,4-dimethoxy- phenyl)-1,4,5,6-tetrahydropyrimidine; ; 1-methyl-2-alkoxycarbonylamino-5-(3,5-dibutoxy- phenyl)-1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5- (2,6-dimethyl- phenyl)-1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5-(2,4-dibutyl- phenyl)-1,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-S- (2, 6-dimethylthio- phenyl)-l,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-5- (2, 4-dimethyl- sulfinylphenyl)-l,4,5,6-tetrahydropyrimidine; l-methyl-2-alkoxycarbonylamino-S- (2, 4-diethyl- sulfonylphenyl)-l,4,5,6-tetrahydropyrimidine; and the like. EXAMPLE 7: 2-Amino-4-phenyl-1,4,5,6- tetrahydropyrimidines A. A solution of l.32g of the dihydrochloride salt of l-phenyl-1,3-propanediamine in a little water is made alkaline with excess of 30% sodium hydroxide and the free diamine is extracted 3 times with toluene. The extracts are combined, the toluene is evaporated and the residue is dissolved in 250ml of methanol. A solution of 0.64g of cyanogen bromide in methanol is added and the mixture is allowed to stand at room temperature for 5 hours and is then refluxed for 1 hour. The solvent is removed under vacuum to give an oil residue which is dissolved in 25ml of isopropanol and the product crystallizes out to give 0.59g of fine needles of 2-amino-4-phenyl-l,4,5,6-tetrahydropyrimidine, mp 192-194 , hydrobromide. B. In a similar manner, by substituting the appropriate 1- (substituted phenyl)-1, 3-propanediamine prepared in accordance with Preparation E for phenyl-1,3-propanediamine, other compounds of this invention are prepared such as 2-amino-4-(2-chlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(3-chlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(4-chlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2-fluorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(3-fluorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4- (4-fluorophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4-(2-bromophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4-(4-bromophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4- (2-iodophenyl)-1,4,5,6-tetrahydro- pyr imidine; ; 2-amino-4-(3-iodophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4- (4-iodophenyl) -1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2,4-dichlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(3,5-dichlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2,5-dichlorophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4-(2,6-dichlorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2,3-difluorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2,4-difluorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2,5-difluorophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4-(2,6-difluorophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(3,5-difluorophenyl)-1,4,5,6-tetrahydro- pyr imidine; ; 2-amino-4-(3,6-dibromophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2,4-dibromophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4-(3,5-dibromophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4-(2,4-diiodophenyl)-1,4,5,6-tetrahydro pyr imidine; 2-amino-4-(2,6-diiodophenyl)-1,4,5,6-tetrahydro pyr imidine; 2-amino-4-(2-trifluoromethylphenyl)-1,4,5,6-tetra- hydropyr imidine; 2-amino-4-(2-methoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(3-methoxyphenyl)-1,4,5,6-tetrahydro- pyrimidine (hydrobromide salt), m.p. 189-191 C 2-amino-4-(4-methoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2-ethoxyphenyl)-1,4,5,6-tetrahydro- pyrimidine; ; 2-amino-4-(3-ethoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(4-ethoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2-propoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(3-propoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(4-propoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(4-butoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(4-methylphenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4-(2-methylphenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4- (3-methylphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4- (3-ethylphenyl) -1,4,5 ,6-tetrahydro- pyrimidine; 2-amino-4-(4-ethylphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2-ethylphenyl)-1,4,5,6-tetrahydro- pyrimidine; ; 2-amino-4-(2-isopropylphenyl}-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(3-isopropylphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(4-isopropylphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2-trifluoromethylphenyl)-1,4,5,6-tetra- hydropyr imidine; 2-amino-4-(3-trifluoromethylphenyl)-1,4,5,6-tetra- hydropyr imidine; 2-amino-4- (4-trifluoromethylphenyl)-1,4,5,6-tetra- hydropyr imidine; 2-amino-4-(2-methylthiophenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(4-methylthiophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4-(2-ethylthiophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4-(4-ethylthiophenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4- (2-butylthiophenyl)-l,4,5,6-tetrahydro- pyrimidine; ; 2-amino-4- (3-butylthiophenyl)-l,4,5,6-tetrahydro- pyr imidine; 2-amino-4- (4-methsulfinylphenyl) -1,4,5,6-tetrahydro- pyr imidine; 2-amino-4- (4-ethylsulfonylphenyl)-l,4,5,6-tetra- hydropyr imidine; 2-amino-4-(2,4-dimethoxyphenyl)-1,4,5,6-tetrahydro- pyr imidine; 2-amino-4-(2,6-diethoxyphenyl)-1,4,5,6-tetrahydro- pyrimidine; 2-amino-4-(3,5-diethylthiophenyl)-1,4,5,6-tetra hydropyr imidine; 2-amino-4-(2,6-dimethylsulfinylphenyl)-l,4,5,6- tetrahydropyrimidine; 2-amino-4-(2,6-dimethylsulfonylphenyl)-l,4,5,6- tetrahydropyrimidine; and the like. EXAMPLE 8: 2-Alkylcarbonylamino-4-phenyl-l, 4,5,6- tetrahydropyr imidines A. By following in principle the procedure of Example 3, Part A but substituting 2-amino-4-phenyl1,4,5,6-tetrahydropyrimidine for 2-amino-5-phenyl-1,4,5,6tetrahydropyrimidine, the corresponding 2-acetamido-4 phenyl-1,4,5,6-tetrahydropyrimidine is obtained. B. Similarly, by following the procedure of Part A of this example but substituting tetrapropionylglycoluril or tetrabutyrylglycoluril for tetracetylglycoluril other amides of this invention are prepared such as 2-propionamido-4-phenyl-1,4,5,6-tetrahydropyrimidine or 2-butyramido-4-phenyl-1,4,5,6-tetrahydropyrimidine. C. Similarly, by following the procedures of Parts A and B of this example, but substituting the other 2-amino-4-phenyl-1,4,5,6-tetrahydropyrimidine of Example 7, Part C for 2-amino-5-phenyl-1,4,5,6-tetrahydropyrim idine, the corresponding 2-acetamido, 2-propionamido or 2-butyramido-4-phenyl-1,4,5,6-tetrahydropyrimidines are prepared. EXAMPLE 9: 2-Alkoxycarbonylamino-4-phenyl 1,4,5 ,6-tetrahydropyrimidines A. 2-Methoxycarbonylamino-4- (4-fluorophenyl) - 1,4,5 ,6-tetrahydropyrimidine. A solution of 0.93 g of l-(4-fluorophenyl)l,3propanediamine and 1.2 g of l,3-bis(methoxycarbonyl)-S- methylisothiourea in 300 ml of methanol is refluxed for 2 hours and then concentrated to 25 ml to give crystalls of 1.02 g of product having a m.p. 209-2140C. Recrystallization of this product from 75 ml of methanol yields 0.8 g of 2-methoxycarbonylamino-4-(4-fluorophenyl)-l,4,5,6- tetrahydropyrimidine, m.p. 211-212 C. The hydrochloride salt is prepared from ethanol containing hydrogen chloride, m.p. 166-1680C. B. Similarly, by following in principle the process of Part A of this example but substituting other l-(optionally substituted phenyl)-1,3-propanediamines prepared according to the process of Preparation G, Part 2 for 1-(3-methoxyphenyl)-1,3-propanediamine, other compounds of this invention are prepared such as 2-methoxycarbonylamino-4-phenyl-1,4,5,6-tetrahydropyrimidine, m.p. 186-1900C; 2-methoxycarbonylamino-4-(2-chlorophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(3-chlorophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(4-chlorophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(2-fluorophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(3-luorophenyl)-lt4t5 tetrahydropyr imidine; ; 2-methoxycarbonylamino-4-(2-bromophenyl)-1,4,5,6- tetr ahydropyr imidine; 2-methoxycarbonylamino-4- (3-bromophenyl)-1,4,5,6- tetrahydropyrimidine; 2-methoxyzarbonylamino-4-(4-bromophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4- (2-iodophenyl) -1,4,5,6- tetrahydropyr imidine; 2-methoxyzarbonylamino-4-(3-iodophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxyearbonylamino-4-(4-iodophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxyearbonylamino-4-(2,4-dichlorophenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxyzarbonylamino-4-(3,5-dichlorophenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4-(2,5-dichlorophenyl)- 1,4,5,6-tetrahydropyrimidine; ; 2-methoxycarbonylamino-4-(2,6-dichlorophenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4-(2,3-difluorophenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4-(2,4-difluorophenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4-(2,5-difluorophenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxyearbonylamino-4-(2,6-difluorophenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4- (3, 5-difluorophenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4-(3,6-dibromophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(2,4-dibromophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4- (3,5-dibromophenyl)-l,4,5,6- tetrahydropyr imidine; ; 2-methoxycarbonylamino-4- (2,4-diiodophenyl)-l,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(2,6-diiodophenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4- (2-methoxyphenyl) -1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(4-methoxyphenyl)-1,4,5,6 tetrahydropyr imidine; 2-methoxycarbonylamino-4-(2-ethoxyphenyl)-1,4,5,6- tetrahydropyrimidine; 2-methoxycarbonylamino-4-(3-ethoxyphenyl)-1,4,5,6- tetrahydropyrimidine; 2-methoxyearbonylamino-4-(4-ethoxyphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methpxycarbonylamino-4-(2-propoxyphenyl)-1,4,5,6- tetrahydropyrimidine; 2-methoxycarbonylamino-4-(3-propoxyphenyl)-1,4,5,6tetrahydropyrimidine; 2-methoxycarbonylamino-4-(4-propoxyphenyl)-1,4,5,6 tetrahydropyr imidine; ; 2-methoxycarbonylamino-4-(4-butoxyphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(2-methylphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(3-methylphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(4-methylphenyl)-1,4,5,6- tetrahydropyrimidine, m.p. 198-20O0C; 2-methoxycarbonylamino-4-(2-ethylphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(3-ethylphenyl)-1,4,5,6- tetrahydropyrimidine; 2-methoxycarbonylamino-4- (4-ethylphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(2-isopropylphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(3-isopropylphenyl)-1,4,5,6tetrahydropyrimidine; ; 2-methoxycarbonylamino-4-(4-isopropylphenyl)-1,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(2-trifluoromethylphenyl)1,4,5,6-tetrahydropyrimidine, m.p. 195-1970C; 2-methoxycarbonylamino-4- (3-trifluoromethylphenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4- (4-trifluoromethylphenyl) - 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4-(2-methylthiophenyl)1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4-(4-methylthiophenyl)1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4-(2-ethylthiophenyl)-l,4,5,6- tetrahydropyrimidine; 2-methoxycarbonylamino-4-(4-ethylthiophenyl)-1,4,5,6 tetrahydropyr imidine; ; 2-methoxycarbonylamino-4-(2-butylthiophenyl)-1,4,5,6 tetrahydropyr imidine; 2-methoxycarbonylamino-4-(3-butylthiophenyl)-l,4,5,6- tetrahydropyr imidine; 2-methoxycarbonylamino-4-(4-methsulfinylphenyl)- 1,4,5 ,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4- (4-ethylsulfonylphenyl) - 1,4,5 ,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4-(2,4-dimethoxyphenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxyzarbonylamino-4-(2,6-diethoxyphenyl)- 1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4- (3,5-diethylthiophenyl) - 1,4,5 ,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4- (2, 6-dimethylsulfinyl- phenyl)-1,4,5,6-tetrahydropyrimidine; 2-methoxycarbonylamino-4- (2, 6-dimethylsulfonyl- phenyl)-1,4,5,6-tetrahydropyrimidine; and the like. C. Similarly, by following in principle the procedures of Part A of this example but substituting other bis-1,3(alkoxycarbonyl)-S-methylisothiourea or mono-l-alkoxycarbonyl-S-methylisothiourea such as l-ethoxycarbonyl-S-methylisothiourea, l-propoxycarbonyl S-methylisothiourea or l-butoxycarbonyl-S-methylisothiourea for bis-l,3- (methoxycarbonyl)-S-methylisothiourea and a suitable l-phenyl-1,3-propanediamine for 1-(4fluorophenyl)-1,3-propanediamine, other 2-alkoxycarbonyl- amino4-phenyl-1,4,5,6-tetrahydropyrimidines are prepared such as 2-ethoxycarbonylamino-4-phenyl-1,4,5,6-tetrahydro pyr imidine; 2-isopropoxycarbonylamino-4-phenyl-1,4,5,6-tetra- hydropyr imidine; ; 2-n-propoxycarbonylamino-4-phenyl-1,4,5,6-tetra- hydropyrimidine, m.p. 134-1370C; 2-n-butoxycarbonylamino-4-phenyl-1,4,5,6-tetrahydro- pyr imidine; 2-n-propoxycarbonylamino-4-(3-bromophenyl)-1,4,5,6 tetrahydropyr imidine; 2-i-propoxycarbonylamino-4- (2, 6-dichlorophenyl) - 1,4,5,6-tetrahydropyrimidine; and the like. EXAMPLE 10 REVERSAL OF RESERPINE-INDUCED HYPOTHERMIA IN MICE The assay was used to evaluate the potential antidepressant activity of compounds of this invention. Male Swiss-Webster Institute for Cancer Research mice weighing 18-24g were utilized for these experiments. The mice, having been in holding quarters for a minimum of 5 days, were placed in plexi-glass cages 17cm by 20cm with sanicel bedding. Five of the 6 groups of 10 mice each, received reserpine, 5mg/kg, i.p. The reserpine (lOmg) was dissolved in 0.06ml glacial acetic acid and 20ml water. The sixth group was not pretreated. Two hours later the mice were dosed with either water or test compound at various doses. The group which had not received the reserpine pretreatment was also dosed with water; consequently a postive and a negative control group were present. The test compounds were administered orally (p.o.) in logarithmically spaced doses. One hour after the oral dosing, body temperatures were taken from 8 mice from each group utilizing a Yellow Springs-Telethermometer unit. Repeated determinations of body temperature occured at 2, 3 and 4 hours post-drug. The percent reversal of the reserpine-induced hypothermia was determined according to the formula: Percent Reversal = Drug x - Reserpine x x 100 and Water P - Wrater x Reserpine x subjected to an analysis of variance (K = average body temperature of mice from the group). Statistically significant reversal of the reserpine-induced hypothermia was used as a criterion for determining the minimum effective dose (MED) of the compound. The results for representative compounds of Formula (I) are presented in Table 1. In Table 1 (as well as Tables 2, 3 and 4), the values for X, Y, etc. refer to Formula (I) while "sub" refers to the position of the tetrahydropyrimidine ring which is substituted. Table 1 EMI76.1 COMPOUND MED Sub X Y R1 A mg/kg 5 2-C1 6-C1 H (CH3)2CHOC(O)- 1.0 4 H 4-F H CH3COC(O)- 1.0 4 H H H H 10.0 5 2-C1 6-C1 H CH30C(O)- 0.15 4 H H H CH30C(O)- 2.5 5 H H H CH30C(O) 0.0006 5 H 3-Br H H- 10.0 5 H 3-Br H CH30C(O)- 1.0 5 2-C1 4-C1 H CH30C(O)- 1.0 4 H H H CH3(CH2)20C(0)- 10.0 5 H 3-Br H CH3(CH)20C(O)- 1.0 5 H H H CH3CH20C(0)- 0.04 4 H 2-CF3 H CH30C(0)- 1.0 4 H 3-CH30 H CH30C(0) 10.0 5 H H H (CH3)2CHOC(0)- 0.04 5 H 2-C1 H CH30C(0)- 10.0 5 H H CH3 CH30C(0)- 0.04 5 H H H H 0.01 5 H 3-MeO H CH30C(O)- 10.0 5 H 4-F H CH3OC(O)- 0.15 EXAMPLE 11 ANTICONVULSANT ACTIVITY - MAXIMAL ELECTROSHOCK TEST This assay was used to evaluate the anticonvulsant activity of compounds of this invention. Groups of 10 male Hilltop ICR mice were utilized for these experiments. At fifteen minutes prior to testing, drug or vehicle was administered intraperitoneally (i.p.). At the appropriate time the mice were subjected to a transcorneal electroshock generated by a stimulator (Woodbury, L.A. and Davenport, V.D.: Design and Use Of A New Electroshock Seizure Apparatus And Analysis Of Factors Altering Seizure Threshold And Pattern. Arch. Intern. Pharmacodyn. They. 92: 97-107,1952). The shock (50 mamp. 0.2sex) elicited three types of seizures: tonic extension, tonic flexion and clonic seizures. For the purposes of this test, the antagonism of the tonic extensor seizure was utilized as an endpoint. The quantal data accumulated from several doses of a test compound were utilized to determine an ED50 (Litchfield, J.F. and Wilcoxon, F.: A Simplified Method of Evaluating Dose-effect Experiments). J. Pharmacol. Exp. Ther. 96: 99-113, 1949). The results for representative compounds are set forth in Table 2. Table 2 EMI78.1 COMPOUNDS ED50 Sub X Y R1 A mg/kg 5 H 3-Br H H- 47 4 H H H CH3(CH2)20C(O)- 30 4 H 2-CF3 H CH30C(0) 44 5 H 4-(CH3)2CE- H CH30C(0) 55 5 H 2-C1 H CH30C(0) 42 5 H 4-F H CH3OC (0) 100 EXAMPLE 12 CENTRALLY ACTING SKELETAL MUSCLE RELAXANT ASSAY CAT LINGUOMANDIBULAR REFLEX PREPARATION This assay is used to assess the centrally acting skeletal muscle relaxant properties of compounds of this invention. Mongrel cats weighing 2-Skg were anesthetized with phenobarbital sodium, 180mg/kg, i.p. The anesthetized cat was placed in a stereotaxic headholder, shaved, and the femoral artery and vein were cannulated. The cannula from the fermoral artery was connected to a Statham Model P-23 AC Transducer in order to monitor blood pressure. The femoral vein was utilized for the administration of drugs. The cat was placed in a prone position and two electrodes, consisting of wound clips soldered to wires, were attached bilaterally to the base of the tongue. These leads were then connected to a Grass S8 stimulator. A Grass FT-03 Transducer was placed beneath the jaw. A round platform approximately 4cm in diameter rested against the lower jaw and conducted the movement of the jaw to the transducer. Signals from the transducers were recorded on a Beckman Polygraph. The stimulator was set to deliver single pulses of 2.5msec duration. A determination was made of the voltage necessary to produce a maximal response. The stimulator was then set at 1 volt higher than this maximal voltage. Upon determination of the supramaximal threshold, the tongue was stimulated every 10 sec. Once the response had ben determined to be stable, drug solution was administered i.v. in logarithmically spaced doses. Each cat received several doses of only one test compound. The doses were always administered in an ascending order. Recovery from an individual dose was allowed prior to the next dose administration. The percent reduction of the jaw opening reflex was utilized for determining the activity of the drug. Comparisons of the relative block of the reflex, the steepness of the dose response curve, and the cardiovascular sequel were evaluated and an ED50 determined. The results for representative compounds are set forth in Table 3. Table 3 ED50 Sub X Y R1 A mg/kg 5 2-C1 4-C1 H CH30C(0)- 25 5 H 3CH30 H CH3OC(O)- 7 EXAMPLE 13 CENTRALLY ACTING SKELETAL MUSCLE RELAXANT ASSAY Antagonism of Etonitazene-Induced Rigidity in Rats This assay is based upon the antagonism of rigidity induced by a pharmacological agent, etonitazene. Rats are pretreated with the test compound and then given 0.0125mg/kg, of etonitazene subcutaneously. At 5, 10 and 15 minutes after the etonitazene, they are evaluated for rigidity' of the trunk (scored 0-3) and hind limbs (scored 0-2). The scores for the control group are added and a mean saline score is determined. The sum of the individual rat's scores is used to determine a % reduction in rigidity: mean saline score - individual score mean saline score x 100 = % reduction Rats having a 60% reduction or greater are considered to exhibit antagonism and quantal data is so derived to calculate an ED50 in mg/kg for each compound tested. (Barnett, A., Goldstein, J., Fiedler, E., and Taber, R.: Etonitazine-Induced Rigidity and its Antagonism by Centrally Acting Muscle Relaxants. Europ. J. Pharmacol. 30: 23-28, 1975). The results are set forth in Table 4. Table 4 ED50 Sub X Y R1 A mg/kg 4 H H H H 53 4 H H H CH3(CH2)2OC(O) 37 EXAMPLE 14 Six groups of male mice (ICR-Simonsen) 5 mice per group, in a weight range of 18-23g were used for this study. 2-Methoxycarbonylamino-5-phenyl-1,4,5,6-tetra- hydropyrimidine, maleate was administered intraperitoneally as a solution (0.2%w/v) in water and behavior observed for 2 hours post drug. Behavioral effects observed were decreased motor activity, ataxia exophthalmia piloerection increased induced activity, dysporea (increased depth and decreased rate of respiration), lacrimation twitching, moderate clonic convulsions and death. The onset of effects was less than five minutes after drug administration with peak activity 10 to 15 minutes after drug. The surviving animals appeared normal 90-120 minutes after drug. Death appeared to result from respiratory failure. The LD50 calculated by the Litchfield Wilcoxson method was 26.Smg/kg (25.0-28.1). The intermediate results are summarized in Table 5, below. Table 5 No. of No. of Group Mice Dose(mg/kg) Deaths 1 5 30 5 2 5 27.5 4 3 5 25 0 4 5 20 0 5 5 15 0 6 5 10 0 Other compounds of this invention exhibit similar toxicity characteristics. EXAMPLE 15 Ingredients Quantity per tablet, mgs. 2-methoxycarbonylamino-5phenyl-1,4,5,6-tetrahydro pyr imidine 25 cornstarch 20 lactose, spray-dried 153 magnesium stearate 2 The above ingredients are thoroughly mixed and pressed into single scored tablets. EXAMPLE 16 Ingredients Quantity per tablet, mgs. l-methyl-methoxycarbonylamino-5-phenyl-1,4,5,6-tetra hydropyr imidine 200 cornstarch 50 lactose 145 magnesium stearate 5 The above ingredients are mixed intimately and pressed into single scored tablets. EXAMPLE 17 Ingredients Quantity per tablet, mgs. 2-methoxycarbonylamino-5 phenyl-1,4,516-tetrahydro- pyr imidine 245 cornstarch 75 lactose 175 magnesium stearate 5 The above ingredients are mixed intimately and pressed into single scored tablets. EXAMPLE 18 Ingredients Quantity per tablet, mgs. 2-isopropoxycarbonylamino5-phenyl-1,4,5,6-tetrahydro pyr imidine 25 lactose 125 The above ingredients are mixed and introduced into a No. 1 hard-shell gelatin capsule. EXAMPLE 19 Ingredients Quantity per tablet, mgs. 2-amino-5-phenyl-tetra hydropyr imidine 300 sucrose 300 The above ingredients are thoroughly mixed and processed into single scored tablets. EXAMPLE 20 Ingredients Quantity per tablet, mgs. l-methyl-2-methoxycarbonyl5-phenyl-1,4,5,6-tetrahydro pyr imidine 254 cornstarch 50 lactose 190 magnesium stearate 6 The above ingredients are mixed intimately and pressed into single scored tablets. EXAMPLE 21 Ingredients Quantity per tablet, mgs. 2-methoxycarbonylamino5-phenyl-1,4,5,6-tetrahydropyrimidine 100 lactose 148 dextrose 2 The above ingredients are mixed and introduced into a hard-shell gelatin capsule. EXAMPLE 22 Ingredients Quantity per tablet, mgs. 2-methoxycar bonylamino- 5-p-fluorophenyl-1,4,5,6 tetrahydropyr imidine 158 lactose 92 The above ingredients are mixed and introduced into a hard-shell gelatin capsule. EXAMPLE 23 An injectable preparation buffered to a pH of 7 is prepared having the following composition: 2-amino-5-phenyl-1,4,5,6tetrahydropyrimidine 0.2 g K2HP04 buffer (0.4 M solution) 2 ml. HC1 (1N) q.s. to pH7 water (distilled sterile) q.s. to 20 ml. EXAMPLE 24 A suppositiory totaling 2.8 grams is prepared having the following composition: 2-methoxycarbonylamino1,4,5,6-tetrahydropyrimidine 25 mg. Witepsol H-15 (triglycerides of saturated vegetable fatty acids; a product of Riches-Nelson, Inc., New York, N.Y.) balance EXAMPLE 25 An oral suspension is prepared having the following composition: 2-methoxycarbonylamino-5phenyl-tetrahydropyrimidine 0.1 g. fumaric acid 0.5 g. sodium chloride 2.0 g. methyl paraben 0.1 g. granulated sugar 25.5 g. sorbitol (70% solution) 12.85 g. Veegum K (Vanderbilt Co.) l.Og. flavoring 0.035 ml. colorings 0.5 mg. distilled water q.s. to 100 ml.

Claims: The subject matter claimed is: 1. A compound selected from the group of compounds represented by the formula EMI86.1 wherein A is H, EMI86.2 where R is alkyl of one through six carbon atoms; X is hydrogen, fluoro, chloro, bromo, iodo, hydroxy, alkoxy of one through four carbon atoms, benzyloxy, alkyl of one through four carbon atoms, alkylthio of one through four carbon atoms, alkylsulfinyl of one through four carbon atoms, alkylsulfonyl of one through four carbon atoms or trifluoromethyl; Y is hydrogen or is the same as X; R1 is hydrogen or alkyl of one through four carbon atoms; and the phenyl substituent carrying the X and Y is at the 4- or 5-position of the tetrahydropyrimidine ring when R1 is hydrogen or is at the 5-position when R1 is alkyl and the pharmaceutically acceptable salts thereof. 2. The compound of Claim 1 wherein A is EMI86.3 and the moiety represented by the formula. EMI86.4 is at the 5 position on the 1,4,5,6-tetrahydropyrimidine ring. 3. The compound of Claim 2 wherein X and Y are each hydrogen, R1 is hydrogen or methyl and R is alkyl of one through three carbon atoms. 4. The compound of Claim 3 wherein X, Y and R1 are each hydrogen and R is methyl, namely 2-methoxy carbonylamino-5-phenyl-l, 4,5, 6-tetrahydropyrimidine. 5. The hydrochloride salt of the compound of Claim 4. 6. The compound of Claim 3 wherein X, Y and R1 are each hydrogen and R is ethyl, namely 2-ethoxycarbonylamino-5-phenyl-1,4,5,6-tetrahydropyrimidine. 7. The compound of Claim 3 wherein X, Y and R1 are each hydrogen and R is isopropyl, namely 2-isopro pOxyCarbonylamino-5-phenyl-1,4,5,6-tetrahydropyrimidine. 8. The compound of Claim 1 wherein X, Y and A are each hydrogen and R1 is hydrogen or methyl. 9. A pharmaceutical composition which comprises a therapeu,tically effective amount of a compound of Claim 1 and at least one pharmaceutically acceptable excipient. 10. A process for preparing substitut tetrahydropyrimidine derivatives, which comprises (a) preparing compounds of Claim 1 or pharmaceutically acceptable hydrogen-anion addition salts thereof, as a racemic mixture or a separate optical isomer, wherein A is hydrogen or R OC(O)-, by reacting a propanediamine, as a racemic mixture or separate optical isomer, of the formula: EMI88.1 with cyanogen bromide or a compound selected from those represented by the group of the formulas EMI88.2 EMI89.1 wherein Z is hydrogen or -COOR, R is alkyl of one through six carbon atoms, R1 is hydrogen or alkyl of one through four carbon atoms, R2 is alkyl of one through five carbon atoms, and M and P are independently chlorine, lower alkoxy of one through six carbon atoms or lower alkylthio one through six carbon atoms; or by (b) reacting a compound of the formula: EMI89.2 or a racemic mixture or a separate c cal isomer, with a carbonate of the formula (RO) EMI89.3 or an alkyl chloroformate of the formula ClCOOR, which X, Y and R are as previously defined and R is alkyl of one through six carbon atoms; or (c) preparing a compound of Claim 1 wherein A is RO(O)-, as a racemic mixture or a separate optical isomer, by (a) reacting a compound of the formula: EMI90.1 as a racemic mixture or a separate optical isomer, with a suitable a compound of the formula RC(O)C1, EMI90.2 in the presence of an activating agent, wherein R is alkyl of one through six carbons and R 6is alkyl of one through six carbon atoms; and, if desired, (d)converting a free base of said compound of Claim 1, as a racemic mixture or a separate optical isomer to a pharmaceutically acceptable hydrogen-anion addition salt thereof; or (e)converting a hydrogen anion addition salt of said compound of Claim 1 to the corresponding free base.

Inventors: MARX, MICHAEL, WEINHARDT, KLAUS KURT
Applicants: SYNTEX (U.S.A.) INC.
Application year: 1980
Main classification: C07D239
IPC codes: C07D239