Organic chemical compounds based upon the urea molecule are disclosed which have potent gastric secretion inhibitory properties. The urea is substituted with a 6 membered heterocyclic substituent containing 2 or 3 heteroatoms, and also with a substituted amino alkyl group. Further substitution is also possible. The compounds have profound effects on the inhibition of gastric secretions in the gastro-intestinal tract, and compositions for such uses are also disclosed.

BACKGROUND OF THE INVENTION 
Excess secretion of gastric acid can cause indigestion and stomach distress 
and, if prolonged, can result in ulcer formation. Treatment of excess 
secretion of gastric acid has heretofore consisted mainly of a bland diet, 
abstinence from certain foods and the use of antacids to neutralize the 
gastric acid after it is secreted into the stomach. An improved method of 
treatment would result from the inhibition of gastric acid secretion. It 
is thus an object of the present invention to provide compounds which 
inhibit gastric acid secretion. Another object is to provide methods for 
the preparation of these compounds. A further object is to provide 
pharmaceutical formulations for the administration of these compounds. 
Still another object is to provide a method to inhibit gastric secretion. 
These and other objects of the present invention will become apparent from 
the following description. 
DESCRIPTION OF THE INVENTION 
The compounds of the instant invention are best described by reference to 
the following structural formula: 
##STR1## 
wherein R is a 6 membered heterocyclic ring system containing 2 or 3 
nitrogen heteroatoms, which heterocyclic ring may be optionally 
substituted with from 1 to 3 of loweralkyl, halo, hydroxy, amino, mono or 
di-loweralkylamino, loweralkoxy or phenylloweralkoxy; 
R.sub.1 and R.sub.2 are independently loweralkyl; 
R.sub.3 and R.sub.4 are independently hydrogen or loweralkyl; 
X is oxygen or sulfur; and 
N is an integer of from 2 to 6, such that the direct linkage between the 
nitrogen atoms is either two or three carbon atoms. 
In the foregoing structural formula R is a heterocyclic moiety consisting 
of 6 membered heterocycles containing 2 nitrogen atoms such as pyrimidine, 
pyridazine and pyrazine; and 6 membered heterocycles containing 3 nitrogen 
atoms referred to as triazines. The heterocyclic group may be optionally 
substituted with from 1 to 3 of loweralkyl, halo, hydroxy, amino or mono 
or di-loweralkylamino, loweralkoxy or phenylloweralkoxy. 
In the instant specification the term "loweralkyl" is intended to include 
those alkyl groups of either straight or branched configuration which 
contain from 1 to 5 carbon atoms. Exemplary of such alkyl groups are 
methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl, pentyl and the 
like. 
The term "halo" or "halogen" is intended to include the halogen atoms 
fluorine, chlorine, bromine and iodine. 
PREFERRED EMBODIMENTS OF THE INVENTION 
The preferred embodiments of the instant invention are realized in the 
foregoing structural formula wherein: 
R is pyrimidinyl, pyridazinyl or pyrazinyl optionally substituted with one 
to three of methyl, chloro or dimethylamino; 
R.sub.1, r.sub.2, r.sub.3 and R.sub.4 are independently methyl, ethyl or 
isopropyl; 
n is 2; and 
X is oxygen. 
Further preferred embodiments are realized when the substituents on the 
pyrimidinyl group consist of 1 or 2 methyl groups or a chloro and 2 methyl 
groups. R.sub.1 and R.sub.2 are isopropyl; and R.sub.3 and R.sub.4 are 
methyl. 
The compounds of the present invention are prepared by reacting an 
appropriately substituted alkylene diamine (II) with an appropriately 
substituted carbamoyl halide or thiocarbamoylhalide (II-A) as described in 
the following reaction scheme: 
##STR2## 
wherein X, n, R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as previously 
defined, and Hal is a halogen. The reaction is generally carried out in an 
inert solvent, preferably an aromatic solvent such as benzene at a 
temperature of from about 20.degree. to 120.degree. C., preferably from 
about 75.degree. to 100.degree. C. Where the reaction temperature exceeds 
the boiling point of the reaction solution, the reaction is carried out 
under pressure. It is preferred to contain in the reaction mixture a 
scavenger for the hydrohalic acid liberated during the course of the 
reaction. Non-reactive bases, either inorganic or organic may be employed 
such as triethylamine, pyridine, sodium carbonate, and the like. The base 
is required in a single molar equivalent to the acid being liberated, 
however, excess base has not been found to be detrimental. The product (I) 
is isolated and purified as the free base or acid addition salt using 
known techniques. The halogen Hal may be any halogen, however, it is 
preferred to use chlorine. 
Optionally the diamine (II) may be converted into an anion before it is 
reacted with the carbamoylhalide. Reactive alkali metal compounds such as 
sodium hydride, lithium aluminum hydride, butyl lithium and the like may 
be employed. The diamine and the alkali metal compound are combined 
preferably at room temperature in the foregoing inert solvent in 
equivalent amounts. If this method is employed the acid scavenger is not 
needed since an alkali metal halide is the reaction by-product. 
The alkylene diamine starting materials (II) for the foregoing processes 
are made from the appropriately substituted heterocyclic amine wherein the 
amine function has been activated by a labile activating group. The 
process is best exemplified by the following reaction scheme: 
##STR3## 
In the foregoing reaction scheme Hal, R, R.sub.1, R.sub.2 and n are as 
previously defined and Z is an activating group. The reaction is carried 
out in the presence of a strong base such as sodium hydride, butyl 
lithium, lithium diisopropylamide and the like, in an appropriate, 
nonreactive solvent such as dimethylformamide, toluene, dioxane, and the 
like. The reaction temperature may be in the range of -70.degree. to about 
160.degree. C. It is preferred, however, that the reaction temperature be 
maintained at from about 0.degree. to 100.degree. C. 
The labile activating group (Z) may be an acyl group readily bonded to the 
amino group and which may be selectively removed therefrom. Examples of 
such groups are acetyl, formyl, and the like. 
The labile activating group is removed hydrolytically with acidic (such as 
aqueous mineral acid) or basic (such as alkali hydroxide) reagents, under 
conditions known to those skilled in this art. 
Alternatively the substituted ethylene diamines (II) are prepared from 
appropriately substituted halo heterocyclic compounds (VI). The halogen 
substituent is displaced by the unsubstituted amino group of an 
appropriately substituted alkylene diamine (VII) as shown in the following 
reaction scheme: 
##STR4## 
R, R.sub.1, R.sub.2, Hal and n are as previously defined. 
The reaction is carried out generally in the absence of a solvent at 
temperatures of from about 50.degree. to 150.degree. C. at from 2 hours to 
as much as one week for difficult reactions. If a solvent is employed it 
must have a sufficiently high boiling point to allow the reaction to 
progress. Dimethylformamide, toluene and xylene are exemplary. Generally 
the reactions are complete in from about 10 hours to 3 days. For those 
reactions requiring a prolonged heating period, a catalyst, cuprous 
chloride, may be employed. The use of catalytic amounts of such catalyst 
will generally reduce the reaction time to within the preferred range. The 
products are isolated using techniques known to those skilled in this art. 
In addition, the substituted alkylene diamines (II) are prepared from an 
appropriately alkoxy or alkythio substituted heterocyclic compound (VIII) 
and the above substituted ethylene diamine (VII) as in the following 
reaction scheme: 
##STR5## 
X, R, R.sub.1, R.sub.2 and n are as previously defined and R.sub.5 is 
loweralkyl, preferably methyl. The reaction is carried out under the 
conditions described in the immediately preceding paragraph, and the 
product is isolated using known techniques. 
The compounds of the present invention where X is oxygen (I-A) are prepared 
by reacting a substituted urea (IX) with the above substituted amino alkyl 
halide (IV) as follows: 
##STR6## 
where R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, Hal and n are as previously 
defined. The reaction is carried out by first preparing the alkyl metal, 
preferably lithium salt of the urea (IX) by treating it with lithium 
hydride in dioxene or butyl lithium in benzene. The reaction is refluxed 
for from 1 to 16 hours and then cooled and the substituted amino 
ethylhalide (IV) added and the reaction refluxed for from 2 to 24 hours. 
The product is isolated during known means. 
The substituted urea compounds (IX) are prepared by reacting an 
appropriately substituted heterocyclic amine (X) with the above 
substituted carbamoyl halide (II-A) wherein X is oxygen according to the 
following reaction scheme: 
##STR7## 
wherein R, R.sub.3, R.sub.4, and Hal are as previously defined. 
The foregoing reaction is carried out by combining the heterocyclic amine 
(X) with two moles of an alkali metal hydride such as sodium hydride or 
lithium hydride in a solvent and refluxing for from 10 minutes to 4 hours. 
The carbamoyl halide reagent is added and the reaction mixture then 
maintained at from room temperature to reflux for from 1/2 to 6 hours. 
Preferred solvents are inert solvents such as benzene, toluene, xylene and 
the like. It is also preferred to have an acid scavenger such as triethyl 
amine or pyridine to neutralize the liberated hydrohalic acid. 
Further, the compounds of the instant invention (I) wherein one of R.sub.3 
or R.sub.4 is hydrogen may be prepared by reacting the above alkylene 
diamine (II) with an appropriately substituted loweralkyl isocyanate or 
isothiocyanate as follows: 
##STR8## 
wherein R, R.sub.1, R.sub.2, X and n are as previously defined and R.sub.3 
is loweralkyl. The reaction is generally carried out at from 0.degree. C. 
to the boiling point of the isocyanate or isothiocyanate reagent. 
Preferably the reaction is stirred at room temperature in an aprotic 
solvent such as benzene, toluene, xylene, tetrahydrofuran and the like, 
for from 10 hours to one week. Generally the reaction is complete in from 
24 to 72 hours. 
The compounds of the present invention where X is oxygen and R.sub.3 and 
R.sub.4 are hydrogen may be prepared by reacting cyanogen bromide with the 
above alkylene diamine (II): 
##STR9## 
The reaction is generally carried out in a solvent such as tetrahydrofuran 
with an acid scavenger such as triethyl amine at from 0.degree. to 
50.degree. C. for from 6 hours to 3 days. The intermediate cyanamide (XI) 
is then hydrolized using acid hydrolysis such as aqueous hydrohalic acids 
at about room temperature for from 5 minutes to 6 hours. Preferably 
hydrochloric acid is employed at from 4 to 8 normal strength. The product 
(I-B) is recovered using known techniques. 
In addition, the compounds of the present invention wherein X is oxygen 
(I-A) may be prepared from an appropriately substituted urethane (XII) and 
ammonia or a substituted amine as follows: 
##STR10## 
wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, and n are as previously 
defined and A is a lower alkyl group, a phenyl group or a phenyl group 
substituted with a non-reactive substituent such as loweralkyl. The 
unsubstituted phenyl group is preferred. The reaction is optionally 
carried out in a solvent such as tetrahydrofuran, at from room temperature 
to the reflux temperature of the reaction mixture. When ammonia is 
employed, concentrated aqueous ammonia is employed and the solvent may be 
omitted. In such cases room temperature is adequate to complete the 
reaction. With substituted amines higher temperatures are beneficial, and 
occasionally temperatures higher than reflux, in a bomb, are also 
beneficial. Temperatures to 150.degree. C. may be employed. The reaction 
is generally complete in from 1 to 24 hours, and the product (I-A) 
recovered using standard techniques. 
The starting urethanes (VII) of the foregoing reaction are prepared from 
the alkylene diamine (II) and a chloroformate ester (XIII) as follows: 
##STR11## 
wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, Hal, n, and A are as 
previously defined. The reaction is carried out in an inert solvent such 
as tetrahydrofuran, benzene, toluene, xylene, and the like at from 
0.degree. to 75.degree. C., preferably room temperature for from 1/2 to 3 
days. An acid scavenger such as triethyl amine or pyridine may also be 
employed, but its use is not required. 
The compounds of this invention may be isolated and used as the free base 
or as a pharmaceutically acceptable acid addition salt. Such salts are 
formed by reaction of the free base with the desired inorganic or organic 
acid. The salts are prepared using methods known to those skilled in this 
art. Exemplary inorganic acids are hydrohalic acids such as hydrochloric 
or hydrobromic, or other mineral acids such as sulfuric, nitric, 
phosphoric and the like. Suitable organic acids are maleic, fumaric, 
tartaric, citric, acetic, benzoic, succinic, isethionic and the like. 
The compounds of the present invention in the described dosages may be 
administered orally, however, other routes such as intra peritoneal, 
subcutaneous, intramuscular or intravenous may be employed. 
The active compounds of the present invention are orally administered, for 
example, with an inert diluent or with an assimilable edible carrier, or 
they may be enclosed in hard or soft gelatin capsules, or they may be 
compressed into tablets, or they may be incorporated directly with the 
food of the diet. For oral therapeutic administration, the active 
compounds of this invention may be incorporated with excipients and used 
in the form of tablets, troches, capsules, elixirs, suppositories, 
suspensions, syrups, wafers, chewing gum, and the like. The amount of 
active compound in such therapeutically useful compositions or 
preparations is such that a suitable dosage will be obtained. The tablets, 
troches, pills, capsules and the like may also contain the following: a 
binder such as gum tragacanth, acacia, corn starch or gelatin; an 
excipient such as dicalcium phosphate; a disintegrating agent such as corn 
starch, potato starch, alginic acid and the like; a lubricant such as 
magnesium stearate; and a sweetening agent such as sucrose, lactose or 
saccharin may be added or a flavoring agent such as peppermint, oil of 
wintergreen, or cherry flavoring. When the dosage unit form is a capsule, 
it may contain in addition to materials of the above type, a liquid 
carrier such as a fatty oil. Various other materials may be present as 
coatings or to otherwise modify the physical form of the dosage unit, for 
instance, tablets, pills or capsules may be coated with shellac, sugar or 
both. A syrup or elixir may contain the active compounds, sucrose as a 
sweetening agent, methyl and propyl parabens as preservatives, a dye and a 
flavoring such as cherry or orange flavor. Of course, any material used in 
preparing any dosage unit form should be pharmaceutically pure and 
substantially non-toxic in the amounts employed.

EXAMPLE 1 
N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N' 
-(4,6-dimethyl-2-pyrimidinyl)urea 
A. 2-(2-Diisopropylaminoethylamino)-4, 6-dimethyl pyrimidine. 
To 600 ml of dry dimethylformamide is added 
2-acetamido-4,6-dimethylpyrimidine (34.8 g., 0.21 mole) and 
2-diisopropylaminoethyl chloride hydrochloride (48 g., 0.24 mole). The 
mixture is stirred under nitrogen and sodium hydride (50% in mineral oil) 
(24.7 g., 0.515 mole) is added in portions over one hour while the 
temperature is maintained below 45.degree. C. The mixture is then heated 
at 75.degree.-78.degree. C. for 1/2 hour and then at 90.degree.-95.degree. 
C. for 31/2 hours. On cooling, ethanol, 25 ml, is added and the solvents 
removed under reduced pressure. The residue is suspended in 75 ml of 
1-propanol and 400 ml of 5N sodium hydroxide and refluxed with stirring 
for 18 hours. On cooling the mixture is extracted with methylene chloride. 
The organic extracts are then extracted with dilute hydrochloric acid. The 
acid extracts are extracted with hexane and then made alkaline with a 
molar excess of sodium hydroxide. The crude product is extracted from the 
basic solution with diethyl ether. The ethereal extracts are washed with 
saturated sodium chloride solution, dried over sodium sulfate and 
concentrated under vacuum. The residue is distilled and the product 
diamine (37.2 g., 0.149 mole) collected at 130.degree.-134.degree. C./0.4 
mm; melting point 79.5.degree.-82.degree. C. 
B. 
N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N'-(4,6-dimethyl-2-pyrimidinylur 
ea 
A mixture of 2-(2-diisopropylaminoethylamino)-4,6-dimethyl pyrimidine (17.0 
g. 0.068 mole) and sodium hydride (50% in mineral oil) (4.19 g., 0.86 
mole) in 175 ml. of dry toluene is stirred under nitrogen at 
85.degree.-95.degree. C. for one half hour and then heated under reflux 
for one half hour. Dimethylcarbamoyl chloride (8.6 g., 0.08 mole) is added 
and heating under reflux is continued for twenty-four hours. The reaction 
is cooled and ethanol (10 ml) and sodium hydroxide (75 ml., 3.3N) are 
added. The aqueous layer is extracted with methylene chloride and the 
extracts are dried over sodium sulfate and concentrated to an oil. The oil 
is distilled at 0.5 mm of Hg and the product boiling at 
155.degree.-158.degree. C. is collected. 
EXAMPLE 2 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(2-pyrazinyl)urea Dihydrobromide 
To a solution of 2-(2-dimethylaminoethylamino) pyrazine (10 g., 0.0601 
mole) and triethylamine (7.2 g., 0.072 mole) in 150 ml of dry benzene is 
added dimethylcarbamoyl chloride (6.93 g., 0.0645 mole) with stirring. The 
mixture is refluxed for 18 hours, cooled to room temperature, diluted with 
100 ml of ether and filtered. The filtrate is concentrated under vacuum 
and the residual oil diluted with 250 ml of petroleum ether, treated with 
charcoal and filtered. Removal of the solvent under reduced pressure gives 
13 g. (0.055 mole) of an amber oil. The oil is dissolved in 250 m. of 
ether and gaseous hydrogen bromide is passed into the solution, the 
precipitated salt is filtered, redissolved in isopropanol and the solution 
concentrated to dryness under reduced pressure. The solid is triturated 
with 35 ml of isopropanol, filtered and recrystallized from ethanol to 
obtain 12.6 g. (0.031 mole) of 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(2-pyrazinyl)urea 
dihydrobromide, melting point 157.5.degree.-159.5.degree. C. 
EXAMPLE 3 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(5,6-dimethyl-2-pyrazinyl)urea 
Dihydrobromide 
A. 2-(2-Dimethylaminoethylamino)-5,6-dimethyl pyrazine. 
2-chloro-5,6-dimethylpyrazine (12.8 g., 0.09 mole) is added to 
unsym-dimethylethylenediamine (26 g., 0.295 mole) containing cuprous 
chloride (0.25 g.) and the mixture is heated for 48 hours in an oil bath 
maintained at 135.degree.-140.degree. C. On cooling, 50 ml of water and a 
single molar excess of 10N sodium hydroxide are added. The mixture is 
extracted with methylene chloride. The organic extracts are backwashed 
with saturated sodium chloride solution, dried over sodium sulfate, 
filtered and concentrated under vacuum. The residual oil is dissolved in 
hexane, filtered and reconcentrated to obtain the product oil (15.8 g., 
0.081 mole). 
B. N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(5,6-dimethyl-2-pyrazinyl)urea 
Dihydrobromide 
Following the process of Example 2 using 
2-(2-dimethylaminoethylamino)-5,6-dimethyl pyrazine there is obtained 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(5,6-dimethyl-2-pyrazinyl)urea 
dihydrobromide, melting point 188.degree. C. 
EXAMPLE 4 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(6-dimethyl-amino-2-pyrazinyl)ure 
a Dihydrochloride 
A. 2-Chloro-6-dimethylaminopyrazine 
Cuprous chloride (50 mg) is added to a solution of dimethylamine (36 g., 
0.8 mole) in 260 ml of isopropanol. 2,6-Dichloropyrazine (49.9 g., 0.33 
mole) is added to the mixture with stirring and cooling to maintain the 
temperature at 35.degree.-40.degree. C. After 3/4 hr. the cooling bath is 
removed and the reaction mixture is stored at ambient temperature for 16 
hours and finally at 42.degree.-48.degree. C. for 3 hours. The solvent is 
removed under vacuum and the residue is dissolved in dilute hydrochloric 
acid. The aqueous solution is extracted with ether and then made basic 
with solid sodium bicarbonate and extracted with methylene chloride. The 
organic extracts are washed with brine, dried over sodium sulfate and 
concentrated under vacuum to obtain 49 g. of product, melting point 
46.degree.-8.degree. C. 
B. 2-(2-Dimethylaminoethylamino)-6-dimethylaminopyrazine. 
Following the process of Example 3A using 2-chloro-6-dimethylaminopyrazine 
there is obtained, 2-(2-dimethylaminoethylamino)-6-dimethylaminopyrazine. 
C. 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(6-dimethylamino-2-pyrazinyl)ure 
a Dihydrochloride 
2-(2-Dimethylaminoethylamino)-6-dimethylaminopyrazine (16.5 g., (0.079 
mole) is dissolved in 150 ml dry toluene under nitrogen and sodium hydride 
(50% in mineral oil) (4.17 g., 0.087 mole) is added. The mixture is heated 
with stirring at 90.degree.-98.degree. C. for 1/2 hour and then refluxed 
for 1/2 hour. After cooling to 35.degree. C. dimethylcarbamoylchloride 
(9.35 g., 0.087 mole) is added and the mixture is refluxed for 3 hours and 
cooled. Ethanol, 5 ml is added and the solvents are removed under reduced 
pressure. The residue is dissolved in dilute hydrochloric acid and 
extracted with ether. The aqueous layer is made alkaline with aqueous 
sodium hydroxide with a cooling bath to maintain the temperature below 
35.degree. C. The alkaline solution is extracted with methylene chloride. 
The organic extracts are washed with saturated sodium chloride solution, 
dried over sodium sulfate and concentrated under vacuum. The residual oil 
is dissolved in isopropanol, 50 ml and diethyl ether, 300 ml and then 
gaseous hydrogen chloride is passed into the solution. The product 
dihydrochloride crystallizes, is filtered, and washed with 100 ml of 1:1 
acetone: isopropanol. Recrystallization from 150 ml isopropanol and 75 ml 
of diethyl ether yields 8 g. (0.029 mole) of the dihydrochloride salt, 
melting point 189.degree. C. (dec). 
EXAMPLE 5 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(4,6-dimethyl-2-pyrimidinyl)urea 
Hydrochloride 
A. 2-(2-Dimethylaminoethylamino)-4,6-dimethylpyrimidine 
Following the procedure of Example 1-A using 2-dimethylaminoethyl chloride 
hydrochloride, there is obtained 
2-(2-dimethylaminoethyl)-4,6-dimethylpyrimidine boiling at 
90.degree.-100.degree. C. at 0.5 mm. 
B. 
N,N-(Dimethyl)-N'-(2-dimethylaminoethyl)-N'-(4,6-dimethyl-2-pyrimidinyl)ur 
ea Hydrochloride 
Following the procedure of Example 2 using 
2-(2-dimethylaminoethylamino)-4,6-dimethylpyrimidine and neutralizing with 
hydrogen chloride instead of hydrogen bromide, 
N,N-(dimethyl-N'-(2-dimethylaminoethyl)-N'-(4,6-dimethyl-2-pyrimidinyl)ure 
a hydrochloride is obtained having a melting point of 
177.degree.-179.degree. C. 
EXAMPLE 6 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(2-pyrimidinyl)urea Hydrochloride 
Following the procedure of Example 2 using 2-(2-dimethylaminoethylamino) 
pyrimidine and neutralizing with hydrogen chloride instead of hydrogen 
bromide, N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-(2-pyrimidinyl)urea 
hydrochloride is obtained having a melting point of 
182.degree.-184.degree. C. 
EXAMPLE 7 
N,N-Dimethyl-N'-(2-dimethylaminoethyl-N'-(4-methyl-6-dimethylamino-2-pyrimi 
dinyl)urea Dihydrobromide 
A. 2-Amino-4-methyl-6-dimethylaminopyrimidine 
2-Amino-4-methyl-6-chloropyrimidine (52 g., 0.36 mole) is heated at 
160.degree. C. for 18 hours with ethanol and an equimolar amount of 
dimethylamine in a pressure vessel. The reaction mixture is evaporated in 
vacuo taken up in 200 ml. of water containg 50 ml. 10N sodium hydroxide 
and 300 ml. of methylene chloride. The mixture is extracted with methylene 
chloride and the organic layer dried and evaporated to dryness in vacuo 
affording 46 g. of 2-amino-4-methyl-6-dimethylaminopyrimidine with a 
melting point of 172.degree.-174.degree. C. 
B. 2-Acetamido-4-methyl-6-dimethylaminopyrimidine 
A mixture of 44 g. (0.29 moles) of 
2-amino-4-methyl-6-dimethylaminopyrimidine 46 g. (0.45 moles) of acetic 
anhydride and 100 ml. toluene is stirred at reflux for 4 hours. The 
reaction mixture is cooled, 25 ml. of ethanol and 100 ml. of hexane are 
added and the mixture is filtered. The filtrate is evaporated in vacuo and 
the residue combined with 200 ml. of methylene chloride and 100 ml. of 
water containing excess ammonium hydroxide. The organic layer is separated 
and the aqueous layer extracted with methylene chloride. The combined 
extracts are dried with sodium sulfate and concentrated to a small volume 
and filtered. The filtrate is concentrated to dryness and taken up in 50 
ml. of methylene chloride and filtered. The solid materials from both 
filtrations are combined affording 48.4 g. of 
2-acetamido-4-methyl-6-dimethylamino pyrimidine melting point 
153.degree.-157.degree. C. 
C. 2-(2-Dimethylaminoethylamino)-4-methyl-6-dimethylaminopyrimidine. 
Following the procedure of Example 1, Part A 
2-acetamido-4-methyl-6-dimethylaminopyrimidine and 2-dimethylaminoethyl 
chloride hydrochloride, 
2-(2-dimethylaminoethylamino)-4-methyl-6-dimethylaminopyrimidine is 
obtained with a boiling point of 120.degree.-124.degree. C. at 0.03 mm. 
D. 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(4-methyl-6-dimethylaminopyrimid 
inyl)urea Dihydrobromide 
Following the procedure of Example 4, Part C using 
2-(2-dimethylaminoethylamino)-4-methyl-6-dimethylaminopyrimidine, and 
hydrogen bromide instead of hydrogen chloride for the final salt formation 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-(4-methyl-6-dimethylamino-2-pyri 
midinyl)urea dihydrobromide is obtained with a melting point of 213.degree. 
C. 
EXAMPLE 8 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(6-chloro-3-pyridazinyl)urea 
Hydrochloride 
A. 3-(2-Dimethylaminoethylamino)-6-chloropyridazine 
Following the procedure of Example 3, Part A using 3,6-dichloropyridazine 
there is obtained 3-(2-dimethylaminoethylamino)-6-chloropyridazine with 
melting point of 86.degree.-92.degree. C. 
B. N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(6-chloro-3-pyridazinyl)urea 
Hydrochloride 
Following the procedure of Example 2 using 
3-(2-dimethylaminoethylamino)-6-chloropyridazine and forming the 
hydrohalide salt of the product with hydrogen chloride there is obtained 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-(6-chloro-3-pyridazinyl)urea 
hydrochloride with melting point of 194.degree. C. 
EXAMPLE 9 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(3-pyridazinyl)urea 
Dihydrochloride 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(6-chloro-3-pyridazinyl)urea 
hydrochloride (10.5 g., 0.034 mole) (Example 8) and 1.5 g. of 5% palladium 
on carbon catalyst are added to a mixture of 35 ml of 2N sodium hydroxide 
in 250 ml of ethyl alcohol. Treatment with hydrogen is performed in a Parr 
apparatus at 40-50 lbs. per sq. in. pressure and ambient temperature. The 
catalyst is removed by filtration, the filtrate is concentrated under 
reduced pressure, water is added and the mixture is extracted with 
benzene. The extracts are concentrated, the residue is dissolved in ether, 
hydrogen chloride is added and 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-(3-pyridazinyl)urea 
dihydrochloride melting at 187.5.degree.-188.5.degree. C. is obtained. 
EXAMPLE 10 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(2,6-dimethyl-4-pyrimidinyl)urea 
Dihydrochloride 
A. 4-(2-Dimethylaminoethylamino)-2,6-dimethyl-pyrimidine 
Following the procedure of Example 3, Part A using 
4-chloro-2,6-dimethylpyrimidine, 
4-(2-dimethylaminoethylamino)-2,6-dimethylpyrimidine is obtained as an oil 
which is vacuum distilled and boils at 108.degree.-111.degree. C. at 0.5 
mm of Hg. 
B. 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(2,6-dimethyl-4-pyrimidinyl)urea 
Dihydrochloride 
Following the procedure of Example 2 using 
4-(2-dimethylaminoethylamino)-2,6-dimethylpyrimidine and forming the 
hydrohalide salt of the product with hydrogen chloride there is obtained 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-(2,6-dimethyl-4-pyrimidinyl)urea 
dihydrochloride with melting point of 220.degree.-222.degree. C. 
EXAMPLE 11 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(3,5,6-trimethyl-2-pyrazinyl)urea 
Dihydrochloride 
A. 2-(2-Dimethylaminoethylamino)-3,5,6-Trimethylpyrazine 
Following the procedure of Example 3, Part A using 
2-chloro-3,5,6-trimethylpyrazine, 
2-(2-dimethylaminoethylamino)-3,5,6-trimethylpyrazine is obtained. 
B. 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(3,5,7-trimethyl-2-pyrazinyl)ure 
a Dihydrochloride 
Following the procedure of Example 2 using 
2-(2-dimethylaminoethylamino)-3,5,6-trimethylpyrazine, and forming the 
hydrohalide salt of the product with hydrogen chloride, 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-(3,5,6-trimethyl-2-pyrazinyl)ure 
a dihydrochloride is obtained with a melting point of 224.degree. C. 
EXAMPLE 12 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(6-methyl-2-pyrazinyl)urea 
Dihydrobromide 
A. 2-(2-Dimethylaminoethylamino)-6-methylpyrazine 
Following the procedure of Example 3, Part A using 
2-chloro-6-methylpyrazine, 2-(2-dimethylaminoethylamino)-6-methylpyrazine 
is obtained as an oil. 
B. N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(6-methyl-2-pyrazinyl)urea 
Dihydrobromide 
Following the procedure of Example 2, using 
2-(2-dimethylaminoethylamino)-6-methylpyrazine,N,N-dimethyl-N'-(2-dimethyl 
aminoethyl)-N'-(6-methyl-2-pyrazinyl)urea dihydrobromide is obtained with a 
melting point of 189.degree. C. 
EXAMPLE 13 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(4-pyrimidinyl)urea 
Dihydrochloride 
A. 4-(2-Dimethylaminoethylamino)pyrimidine 
A solution of 4-methoxypyrimidine (12.9 g., 0.117 mole) and 
unsym-dimethylethylene diamine (20.7 g., 0.23 mole) in 40 ml of xylene is 
heated under reflux for 64 hours. The reaction is concentrated and the oil 
is distilled at 15 mm of Hg. 4-(2-Dimethylaminoethylamino)pyrimidine, 
boiling at 164.degree.-169.degree. C., is collected. 
B. N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(4-pyrimidinyl)urea 
Dihydrochloride 
Following the procedure of Example 2, using 
4-(2-dimethylaminoethylamino)pyrimidine and forming the hydrohalide salt 
of the product with hydrogen chloride, there is obtained 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-(4-pyrimidinyl)urea 
dihydrochloride with a melting point of 206.degree.-208.degree. C. 
EXAMPLE 14 
N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N'-(2-pyrazinyl)urea 
Dihydrobromide 
A. 2-(2-Diisopropylaminoethylamino)pyrazine 
Following the procedure of Example 3, Part A using 2-chloropyrazine and 
unsym-diisopropylethylenediamine, 2-(2-diisopropylaminoethylamino)pyrazine 
is obtained with a boiling range of 180.degree.-190.degree. C. upon 
distillation at 17 mm. of Hg. 
B. N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N'-(2-pyrazinyl)urea 
Dihydrobromide 
Following the procedure of Example 4, Part C using 
2-(2-diisopropylaminoethylamino)pyrazine and forming the hydrohalide salt 
with hydrogen bromide, 
N,N-dimethyl-N'-(2-diisopropylaminoethyl)-N'-(2-pyrazinyl)urea 
dihydrobromide with melting point of 186.degree.-188.degree. C. is 
obtained. 
EXAMPLE 15 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(6-chloro-2-pyrazinyl)urea 
Hydrobromide 
A. 2-(2-Diethylaminoethylamino)-6-Chloropyrazine 
Following the procedure of Example 3, Part A using 2,6-dichloropyrazine, 
2-(2-dimethylaminoethylamino)-6-chloropyrazine is obtained as an oil. 
B. N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(6-chloro-2-pyrazinyl)urea 
Hydrobromide 
Following the procedure of Example 2, using 
2-(2-dimethylaminoethylamino)-6-chloropyrazine, 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-(6-chloro-2-pyrazinyl)urea 
hydrobromide with a melting point of 159.5.degree.-161.degree. C. is 
obtained. 
EXAMPLE 16 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(3,6-dimethyl-2-pyrazinyl)urea 
A. 2-(2-Dimethylaminoethylamino)-3,6-dimethylpyrazine 
Following the procedure of Example 3, Part A using 
2-chloro-3,6-methylpyrazine, 
2-(2-dimethylaminoethylamino)-3,6-dimethylpyrazine is obtained as an oil 
which is distilled at 0.5 mm of Hg. and collected at a boiling point of 
89.5.degree.-91.5.degree. C. 
B. N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(3,6-dimethyl-2-pyrazinyl)urea 
Following the procedure of Example 2 using 
2-(2-dimethylaminoethylamino)-3,6-dimethylpyrazine and omitting 
hydrohalide salt formation, 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-(3,6-dimethyl-2-pyrazinyl)urea 
is obtained with melting point of 96.degree.-98.degree. C. 
EXAMPLE 17 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-[3-(1,2,4-triazinyl)]urea 
Hydrochloride 
A. 3-(2-Dimethylaminoethylamino)-1,2,4-triazine 
3-Methylthio-1,2,4-triazine (19.1 g., 0.15 mole) and unsym-dimethylethylene 
diamine (35.2 g., 0.40 mole) are dissolved in 100 ml of isopropyl alcohol 
and the mixture is heated under reflux in a nitrogen atmosphere for five 
days. The solvent is removed under reduced pressure and the residue is 
distilled at 0.5 mm of Hg. 3-(2-Dimethylaminoethylamino)-1,2,4-triazine is 
collected at 168.degree.-169.degree. C. 
B. N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-[3-(1,2,4-triazinyl)]urea 
Hydrochloride 
Following the procedure of Example 2, using 
3-(2-dimethylaminoethylamino)-1,2,4-triazine and forming the hydrohalide 
salt of the product with hydrogen chloride, there is obtained 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-[3-(1,2,4-triazinyl)] urea 
hydrochloride with melting point of 192.degree.-193.degree. C. 
EXAMPLE 18 
N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N'-(4-methyl-6-benzyloxy-2-pyrimi 
dinyl)urea 
A. 2-Amino-4-methyl-6-benzyloxypyrimidine 
2-Amino-4-methyl-6-hydroxypyrimidine (62.5 g., 0.50 mole) is dissolved in 
500 ml of dimethylformamide and sodium hydride (0.5 mole) is added over a 
1 hour period under a nitrogen atmosphere. The mixture is heated at 
75.degree. C. for 11/2 hours. Benzyl chloride (69.3 g., 0.55 moles) is 
then added over 15 minutes and the mixture is heated at 90.degree. C. and 
stirred for 11/2 hours. After cooling, the reaction mixture is filtered 
and concentrated under vacuum to an oil from which 
2-amino-4-methyl-6-benzyloxypyrimidine melting at 
108.degree.-109.5.degree. C. is obtained by crystallization from n-butyl 
chloride. 
B. 2-Acetamido-4-methyl-6-benzyloxypyrimidine 
Acetic anhydride (15.3 g., 0.15 mole) is added to a stirred suspension of 
2-amino-4-methyl-6-benzyloxypyrimidine (23.6 g., 0.11 mole) in 150 ml of 
benzene. The mixture is heated at reflux for 4 hours. It is cooled, 
neutralized with aqueous sodium carbonate and the benzene layer separated. 
The benzene solution is concentrated under vacuum to an oil from which 
2-acetamido-4-methyl-6-benzyloxy-pyrimidine melting at 
121.degree.-122.degree. C. is isolated by crystallization from hexane 
n-butyl chloride. 
C. 2-(2-Diisopropylaminoethylamino)-4-methyl-6-hydroxy-pyrimidine 
Following the procedure of Example 1 part A using 
2-acetamido-4-methyl-6-benzyloxypyrimidine and conducting the final 
hydrolysis with 3N hydrochloric acid, there is obtained 
2-(2-diisopropylaminoethylamino)-4-methyl-6-hydroxypyrimidine. 
D. 2-(2-Diisopropylaminoethylamino)-4-methyl-6-benzyloxy-pyrimidine 
Following the procedure of part A using 
2-(2-diisopropylaminoethylamino)-4-methyl-6-hydroxypyrimidine, 
2-(2-diisopropylaminoethylamino)-4-methyl-6-benzyloxypyrimidine is 
obtained as an oil which is distilled at 0.6 mm of Hg and is collected at 
198.degree.-200.degree. C. 
E. 
N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N'-(4-methyl-6-benzyloxy-2-pyrim 
idinyl)urea 
Under a nitrogen atmosphere, n-butyl lithium solution (22.2 ml, 0.036 mole) 
is added dropwise with stirring to a solution of 
2-(2-diisopropylaminoethylamino)-4-methyl-6-benzyloxypyrimidine (12.4 g., 
0.036 mole) in 75 ml. of dry benzene at 25.degree. to 30.degree. C. with 
occasional cooling over a 20 minute period. After stirring an additional 
3/4 hour, dimethylcarbamoyl chloride (4.3 g., 0.04 mole) is added dropwise 
over 15 minutes. The reaction is stirred at room temperature for 16 hours. 
After cooling, the reaction mixture is treated with water and the benzene 
layer is separated. The crude product is extracted into 1N-hydrochloric 
acid. This aqueous solution is basified and the product is extracted into 
ether, dried over sodium sulfate, filtered and concentrated in vacuo. 
Chromatography on silica gel eluting with 25% methanol, 75% chloroform 
yields N,N-dimethyl-N'-(2-diisopropylaminoethyl)-N 
-(4-methyl-6-benzyloxy-2-pyrimidinyl)urea. 
EXAMPLE 19 
N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N'-(4-methyl-6-hydroxy-2-pyrimidi 
nyl)urea Hydrochloride 
N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N'-(4-methyl-6-benzyloxy-2-pyrimi 
dinyl) urea (3.4 g., 0.0082 mole) is dissolved in 50 ml of ethyl alcohol 
and 0.3 g. of 10% palladium on carbon catalyst is added. Hydrogenolytic 
debenzylation is conducted at 30 lbs. per sq. in., the catalyst is 
removed, hydrogen chloride is added and 
N,N-dimethyl-N'-(2-diisopropylaminoethyl)-N'-(4-methyl-6-hydroxy-2-pyrimid 
inyl)urea hydrochloride melting (dec.) at 198.degree.-208.degree. C. is 
obtained. 
EXAMPLE 20 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(5-chloro-2-pyrimidinyl)urea 
Dihydrobromide 
A. 2-(2-Dimethylaminoethylamino)-5-chloropyrimidine 
Following the procedure of Example 1 part A and replacing the 
2-acetamido-4,6-dimethylpyrimidine and 2-diisopropylaminoethyl chloride 
hydrochloride with equivalent amounts of 2-acetamido-5-chloropyrimidine 
and 2-dimethylaminoethyl chloride hydrochloride respectively, there is 
obtained 2-(2-dimethyl-aminoethylamino)-5-chloropyrimidine which is 
distilled at 115.degree.-118.degree. C. at 1.8 mm of mercury. 
B. N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(5-chloro-2-pyrimidinyl)urea 
Dihydrobromide 
Following the procedure of Example 18 part E using 
2-(2-dimethylaminoethylamino)-5-chloropyrimidine and forming the 
hydrohalide salt of the product with hydrogen bromide, 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-(5-chloro-2-pyrimidinyl)urea 
dihydrobromide melting at 182.degree. C. is obtained. 
EXAMPLE 21 
N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N'-(4,6-dimethyl-5-chloro-2-pyrim 
idinyl)urea Hydrochloride 
A. N,N-Dimethyl-N'-(4,6-dimethyl-5-chloro-2-pyrimidinyl)urea 
Sodium hydride (6 g., 55%, 0.137 mole) is added to a mixture of 
2-amino-4,6-dimethyl-5-chloropyrimidine (19.5 g., 0.125 mole) in 250 ml of 
toluene. The mixture, under a nitrogen atmosphere is heated to reflux and 
stirred for one hour. Another portion of sodium hydride (6 g., 55%, 0.137 
mole) is added and after two hours of reflux, dimethyl carbamoyl chloride 
(13.9 g., 0.125 mole) is added. After one hours of reflux the reaction is 
cooled, water is added, the toluene is removed by vacuum concentration and 
the product is extracted into petroleum ether from which it is 
crystallized by evaporation. 
N,N-Dimethyl-N'-(4,6-dimethyl-5-chloro-2-pyrimidinyl)urea melting at 
127.degree.-129.degree. C. is obtained. 
B. 
N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N'-(4,6-dimethyl-5-chloro-2-pyri 
midinyl)urea Hydrochloride 
The product of part A (12.8 g., 0.056 mole) is dissolved in 185 ml of 
dioxane, lithium hydride (1.16 g., 0.146 mole) is added and the mixture is 
stirred under nitrogen at reflux. Diisopropylaminoethyl chloride 
hydrochloride (11.2 g., 0.056 mole) is added and the mixture is heated 
under reflux for eight hours. Water (20 ml) and isopropyl alcohol (20 ml) 
are added and the mixture is concentrated in vacuo. Water (100 ml) and 
saturated sodium carbonate are added and the mixture is extracted with 
methylene. The combined extract is concentrated, ethanolic hydrogen 
chloride is added and 
N,N-dimethyl-N'-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-5-chloro-2-pyrim 
idinyl)urea hydrochloride is crystallized from ether. The melting point is 
202.degree.-204.degree. C. 
EXAMPLE 22 
N-(2-Diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyrimidinyl)urea 
A. Phenyl 
N-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyrimidinyl)carbamate 
Hydrochloride 
A solution of 2-(2-diisopropylaminoethylamino)-4,6-dimethylpyrimidine (12.5 
g., 0.05 mole) in 50 ml of benzene is added to a solution of phenyl 
chloroformate in 50 ml of benzene. After 72 hours, the solid product is 
collected and recrystallized from acetone to give phenyl 
N-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyrimidinyl)carbamate 
hydrochloride melting at 190.degree.-202.degree. C. 
B. N-(2-Diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyrimidinyl)urea 
Concentrated ammonia (10 ml) is added to a solution of phenyl 
N-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyrimidinyl)carbamate 
hydrochloride (7.33 g., 0.018 mole) in 50 ml of tetrahydrofuran and the 
mixture is allowed to stand for twenty-four hours. It is concentrated, 
water and chloroform are added to the residue, the chloroform is separated 
and concentrated. Crystallization of the residue from hexane yields 
N-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyrimidinyl)urea melting at 
134.degree.-136.degree. C. 
EXAMPLE 23 
N-(2-Dimethylaminoethyl)-N-(2-pyrazinyl)urea 
A. N-(2-Dimethylaminoethyl)-N-(2-pyrazinyl)cyanamide 
A solution of cyanogen bromide (15.9 g., 0.150 mole) in 75 ml of 
tetrahydrofuran is added to a solution of 
2-(2-dimethylaminoethylamino)pyrazine (16.6 g., 0.1 mole) and 
triethylamine (20.9 g., 0.15 mole) in 100 ml of tetrahydrofuran. After 72 
hours, dilute sodium hydroxide is added and the mixture is extracted with 
ether. The extracts are concentrated and the residue is distilled under 
reduced pressure. N-(2-Dimethylaminoethyl)-N-(2-pyrazinyl)cyanamide 
boiling at 130.degree.-132.degree. C. at 0.7 mm is collected. 
B. N-(2-Dimethylaminoethyl)-N-(2-pyrazinyl)urea 
N-(2-Dimethylaminoethyl)-N-(2-pyrazinyl)cyanamide (2.83 g., 0.015 mole) is 
dissolved in 20 ml of 6N hydrochloric acid. After one hour, the mixture is 
made alkaline with concentrated sodium hydroxide and concentrated. The 
residue is extracted with ether which is concentrated. The residue is 
crystallized from butyl chloride and 
N-(2-dimethylaminoethyl)-N-(2-pyrazinyl)urea melting at 
105.degree.-108.degree. C. is obtained. 
EXAMPLE 24 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-[5,6-dimethyl-3-(1,2,4-triazinyl) 
]urea Hydrochloride 
A. 3-(2-Dimethylaminoethylamino)-5,6-dimethyl-1,2,4-triazine 
Following the procedure of Example 17 part A using 
3-methylthio-5,6-dimethyl-1,2,4-triazine, 
3-(2-dimethylaminoethylamino)-5,6-dimethyl-1,2,4-triazine is obtained with 
a melting point of 46.degree.-49.degree. C. 
B. 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-[5,6-dimethyl-3-(1,2,4-triazinyl 
)]urea Hydrochloride 
Following the procedure of Example 2 using 3-(2-dimethylaminoethylamino) 
5,6-dimethyl-1,2,4-triazine and forming the hydrohalide salt of the 
product with hydrogen chloride, there is obtained 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-[5,6-dimethyl-3-(1,2,4-triazinyl 
)]urea hydrochloride melting at 173.degree.-175.degree. C. 
EXAMPLE 25 
N-(2-Dimethylaminoethyl)-N-(4,6-dimethyl-2-pyrimidinyl)-N'-ethylurea 
Hydrochloride 
A solution of 11.6 g., (0.06 mole) of 
2-(2-dimethylaminoethylamino)-4,6-dimethylpyrimidine in 150 ml. of benzene 
is dried by azeotropic distillation. The solution is then treated with 8.5 
g. (0.120 mole) of ethyl isocyanate and heated at reflux for 24 hours. 
After removal of the solvent, the residue is dissolved in 100 ml of ethyl 
ether and the solution is neutralized with 3 ml of 10.6 N hydrogen 
chloride in ethanol. The resulting white precipitate is recrystallized 
from isopropanol to give 
N-(2-dimethylaminoethyl)-N-(4,6-dimethyl-2-pyrimidinyl)-N'-ethylurea 
hydrochloride. 
EXAMPLE 26 
N,N-Dimethyl-N'-(2-dimethylaminoethyl)-N'-(3,6-dimethyl-2-pyrazinyl)thioure 
a 
A solution of 11.6 g. (0.06 mole) of 
2-dimethylaminoethylamino-3,6-dimethylpyrazine in 175 ml of dry 
tetrahydrofuran is allowed to react with 40.8 ml (0.066 mole) of 1.62 M 
butyl lithium in hexane. Then 8.16 g. (0.066 mole) of dimethyl 
thiocarbamoyl chloride in 75 ml of dry tetrahydrofuran is added over 20 
minutes with ice cooling. The reaction mixture is allowed to stir 
overnight at room temperature. After quenching with water, the product is 
extracted into ether. The ether extract is washed with water and saturated 
sodium chloride solutions and dried over magnesium sulfate. The crude 
product is obtained as a brown oil. 
The crude product is chromatographed on silica gel, eluting with 5% 
methanol in chloroform. After combining the appropriate fractions, the 
solvent is removed in vacuum and the residue distilled through a short 
path still. There is obtained 
N,N-dimethyl-N'-(2-dimethylaminoethyl)-N'-(3,6-dimethyl-2-pyrazinyl)thiour 
ea. 
EXAMPLE 27 
N-(2-Dimethylaminoethyl)-N-(2-pyrazinyl)-N'-methylthiourea Hydrochloride 
Following the procedure of Example 25 using 
2-(2-dimethylaminoethylamino)pyrazine and methylisothiocyanate, there is 
obtained N-(2-dimethylaminoethyl)-N-(2-pyrazinyl)-N'-methylthiourea 
hydrochloride. 
EXAMPLE 28 
N,N-Dimethyl-N'-(2-methyl-3-dimethylaminopropyl)-N'-(5-chloro-2-pyrimidinyl 
)urea 
A. 2-(2-Methyl-3-dimethylaminopropylamino)-5-chloropyrimidine 
Following the procedure of Example 1 part A using 
2-acetamido-5-chloropyrimidine and 2-methyl-3-dimethylaminopropyl chloride 
hydrochloride, there is obtained 
2-(2-methyl-3-dimethylamino-propylamino)-5-chloropyrimidine. 
B. 
N,N-Dimethyl-N'-(2-methyl-3-dimethylaminopropyl)-N'-(5-chloro-2-pyrimidiny 
l)urea 
Following the procedure of Example 1 part B using 
2-(2-methyl-3-dimethylaminopropylamino)-5-chloropyrimidine there is 
obtained 
N,N-dimethyl-N'-(2-methyl-3-dimethylaminopropyl)-N'-(5-chloro-2-pyrimidiny 
l)urea. 
EXAMPLE 29 
N,N-Dimethyl-N'-(2-methyl-2-dimethylaminopropyl)-N'-(4-methyl-6-dimethylami 
no-2-pyrimidinyl)urea 
A. 
2-(2-Methyl-2-dimethylaminopropylamino)-4-methyl-6-dimethylaminopyrimidine 
Following the procedure of Example 1 part A using 
2-acetamido-4-methyl-6-dimethylaminopyrimidine and 
2-methyl-2-dimethylaminopropyl chloride hydrochloride, there is obtained 
2-(2-methyl-2-dimethylaminopropylamino)-4-methyl-6-dimethylaminopyrimidine 
. 
B. 
N,N-Dimethyl-N'-(2-methyl-2-dimethylaminopropyl)-N'-(4-methyl-6-dimethylam 
ino-2-pyrimidinyl)urea 
Following the procedure of Example 1 part B using 
2-(2-methyl-2-dimethylaminopropylamino)-4-methyl-6-dimethylaminopyrimidine 
, there is obtained 
N,N-dimethyl-N'-(2-methyl-2-dimethylaminopropyl)-N'-(4-methyl-6-dimethylam 
ino-2-pyrimidinyl)urea. 
EXAMPLE 30 
N,N-Diethyl-N'-(2-diisopropylaminoethyl)-N'-(2-pyrazinyl)urea Hydrochloride 
Following the procedure of Example 4 part C using 
2-(2-diisopropylaminoethylamino)pyrazine and diethylcarbamoylchloride, 
there is obtained 
N,N-diethyl-N'-(2-diisopropylaminoethyl)-N'-(2-pyrazinyl)urea 
hydrochloride.