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Патент USA US3045025

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States Patent 0
_
3,045,015
Patented July 17, 1962
1
2
R:
3,045,015
TRIAZOL0-[2,3-c]-PYRIMIDINES
George William Miller and Francis Leslie Rose, Maccles
?eld, England, assignors to Imperial Chemical Indus
N
R8
gies Limited, London, England, a corporation of Great
ritain
.
No Drawing. Filed Sept. 8, 1959, Ser. No. 838,413
Claims priority, application Great Britain Oct. 3, 1958
8 Claims. (Cl. 260--256.4)
wherein R1, R2 and K, have the meaning stated above,
‘ (except when R1 and R2 stand for amino or mono- or di-.
.
alkylamino radicals) or a salt thereof, with cyanogen
10 halide.
This invention relates to new organic compounds and
A convenient cyanogen halide ‘for use in the above
more particularly it relates to new pyrimidine derivatives
which possess valuable therapeutic properties.
process is cyanogen chloride or cyanogen bromide. The
said reaction may be carried out in the presence of an
inert diluent or solvent for example’water or ethanol.
These
compounds are also useful as intermediates in the prepa
ration of related s-tnazolo-[2,3—c]-Pyrimidine deriva 15 When the hydrazine derivative in the said process is used
as the free ‘base, the process may be carried out in the
According‘to the ‘invention we provide pyrimidine
presence of an acid for. example dilute hydrochloric or
derivatives, one tautomeric form of Whichhas the
acetic acid in order to effect salt formation and‘ solution
formula:
of the hydrazine derivative.
‘
20
The hydrazine derivatives used as starting material may ,
be obtained by interaction of the corresponding halogeno
tives.
,
.
pyrimidines for example the'chloropyrimidines or the
corresponding alkylthiopyrimidines and hydrazine con
veniently in the presence of a diluent or solvent for exam
25
ple water, ethanol or fi-ethoxyethanol. The halo'geno
pyrimidines themselveaforexample the chloropyrimi
dines mentioned above, may be 'obtained'by, interaction
‘we.
of the corresponding hydroxypyrimidines and a 'phos
phorus oxyhalide for example phosphorus oxychloride.
wherein R1, ‘R2 and R3 which may be the same or dif
ferent, stand for hydrogenor for alkyl, optionally sub- >
stituted by hydroxy, alkoxy or halogen radicals, alkenyl
or cyoloalkyl radicals, R1 and R2 which may be the
According to a further feature of the invention we pro
vide a process for the manufacture of those .compounds
_ of the formula stated above wherein one» of the sub
stituents R1 landyRz stands ‘for an aminoor-amono- or di
same or different, stand for amino or mono or dialkyl
alkylamino radical which comprises reacting a pyrimi:
amino ‘radicals, R1 stands for a phenyl or an alkylthio
dine derivative of. the formula:
radical, R2 stands for alkoxy or halogen radicals, R3
,
,
RE
I
stands for a halogen radical or R2 and R3 may be joined
together to form a polymethylene radical, and the acid
addition salts thereof.
Preferred compounds are those wherein the'substituent 40
,gl
(R3) stands for hydrogen and the substituents (R1 and
R2), the same or different, stand for alkyl radicals. Par
ticularly valuable compounds are those wherein the sub
stituent (R3) stands for hydrogen and the substituents
(R1) and (R2), which maybe the same or different, stand 45 wherein of R4Land R5, one stands'for an alkylthio radi- ’
cal or for a halogen radical and the other stands~for‘hy~
for methyl, ethyl, n-propyl or n-butyl radicals. A valu
drogen or for an alkyl radical and R3 “has the meaning
able compound Ipossessing bronchodilatory and respira
stated above, with ammonia or with a mono- or di-alkyl
amine at an elevated temperature and pressure.
p
tory stimulant action is 'Z-amino-5-n-propyl-7-methyl-s
triazolo-[2,3-c1-pyrimidine and ‘a’ valuable compound
The reaction is preferably carried out in the presence ‘of
possessing action against rheumatoid arthritis is Z-amino 50
a diluent or solvent for ‘example ethanol and at a temper
5,7-di-n-propyl-s-triazolo-[2,3-c] pyrimidine. Other valu
ature above 90° C.
‘
g
able compounds possessing broncho'dilatory action are
It is to be under-stood that the pyrimidine derivative
2-amino~5-n-propyl~7-n-butyl- and 2-amino-5-n-propyl-7
ethyl-s-triazolo-[2,3-c]pyrimidine.
’
used as starting material in this process may be replaced ‘ ' ‘4
’
by the corresponding isomeric compound which‘ is obtain
able from the corresponding pyrimidylhydrazine wherein
. It is to be understood that the compounds of the pres
ent invention of the ‘formula statedabove have a skele
. one of the, substituents (R1 and R2) is an alkylthio or a
ton ring structure of the formula:
N678
i
halogen radical by reaction with cyanogen chloride under '
essentially neutral conditions for example in a ‘buffered ‘
60 medium which is preferably a mediumrcontaining acetic
acid and sodium acetate.
4 \\
'
>
-
' vide
. 7 According
a process
to afor
further
the manufacture
feature of theof
invention
the pyrimidine
we pro‘ Y‘ e :
NlN
derivatives which comprises ring closure of a compound"
which is s-triazolo-[4,3-c]pyrimidine, the positions of
65 of the formula:
the carbon and nitrogen atoms :being- numbered as shown.
According to a further feature of the invention we pro-'
vide a process for the manufacture of the said pyrimidine
derivatives with which this invention is concerned which
comprises interacting a pyrimidylhydrazine derivative of 70
the formula:
R7
N/\ R,
, R IMETH
I
Ra—NH
’
3,045,015
3
4.
wherein R3 has the meaning stated above, R6 and R7
stand for alkyl or for halogen radicals and R8 stands for
the radical-—CONH2, -—CSNH2 or -——C(NH).S.Alk (in
The compounds of the present invention are valuable
in that they possess a variety of therapeutic properties.
Thus they are bronchodilators and respiratory stimulants
the form of a salt) wherein Alk stands for an alkyl radi
cal.
other respiratory dysfunctions. The compounds possess
and are therefore useful in the treatment of asthma and
antibacterial activity.
The said ring closure with the compounds wherein R8
stands for the radical —CONH2 is preferably carried out
by heating with a phosphorus oxyhalide for example
phosphorus oxychloride.
They inhibit the formation of
granulomata and are therefore useful in the treatment
of rheumatoid arthritis. They also possess sedative and
hypotensive properties.
.
The ring closure with the compounds wherein R8 10 According to a further feature of the invention there
fore we provide pharmaceutical compositions comprising
stands for the radical —CSNH2 or —~C(-NH).S.Alk (in
as active ingredient one or more of the pyrimidine
the form of a salt) is preferably carried out by heating
derivatives of the formula stated above in admixture
with a desulphurisiing agent for example litharge in the
with a non-toxic pharmaceutical carrier or diluent there
presence of a solvent or diluent for example p-ethoxy
ethanol.
According to a further feature of the invention we
provide a process for the manufacture of the pyrimidine
for.
by which the active ingredient can be administered in
the form of a solid composition for example as a table,
derivatives, which comprises heating a compound of the
formula:
.
Particularly useful compositions are oral compositions
pill or capsule or a liquid composition for example as
20 a solution or suspension.
N
R’iN/ NHNH:
wherein R’ and R” stand for alkyl radicals with a com
pound of the formula:
The said compositions are
preferably formulated so that when the compositions are
used as bronchodilators, each dosage unit contains be
tween 1 mg. and 500 mg., preferably between 10 mg. and
100 mg. of active ingredient and when the compositions
25 are used in the treatment of rheumatoid arthritis, each
dosage unit contains between 10 mg. and 750 mg., prefer
ably between 200 mg. and 500 mg. of active ingredient.
The invention is illustrated but not limited by the fol
Y and Z stand for hydrogen or for lower alkyl radicals.
lowing examples in which the parts are by weight:
Example 1
A stream of cyanogen chloride, previously washed with
According to a further feature of the invention we pro
vide a process for the manufacture of those compounds
.methyl-G-hydrazinopyrimidine in 20 parts of ethanol,
the presence of a diluent or solvent for example ethanol.
one hour at 0° C. and is then ?ltered. The solid residue
preferably in the form of a salt thereof, wherein X stands 30
for an amino radical or for a lower alkylthio radical and
water, is bubbled through a solution of 2.5 parts of 4
of the invention wherein R3 stands for an alkyl radical 35 which is maintained at a temperature of 25-30° C. until
1.4 parts of the gas are absorbed. The resulting solu
optionally substituted by hydroxyl or halogen radicals
tion is sealed and then kept for one hour at 18-22“ C.
which comprises addition of hydrogen, hydroxyl or halo
The reaction mixture is then evaporated to dryness under
gen radicals respectively to the corresponding compound
reduced pressure below 30° C. and the solid residue is
wherein R3 stands ‘for an alkenyl radical.
The said addition of hydrogen may be carried out 'by 40 dissolved in 10 parts of water and treated with 5 parts
of crystalline sodium acetate. The mixture is cooled for
reduction of the alkenyl compound with hydrogen in
is Washed thoroughly with water, dried at 60° C. and is
then crystallised from ethanol. There is thus obtained
The addition of hydroxyl radicals may conveniently be
brought about by oxidation of the alkenyl compound by
means of potassium permanganate in a liquid medium for 45 2-amino-7-methyl-s-triazolo-[2,3-c1-pyrimidine as a col
ourless crystalline solid, M.P. 160° C. '
example in the presence of aqueous acetone. The addi-'
tion of halogen radicals may be. brought about by re
Example 2
action of the alkenyl compound with halogen for exam
ple bromine in the presence of a diluent for example
aqueous acetic acid.
6.9 parts of 2:4-dimethyl-6~hydrazino-pyrimidine are
dissolved in 50 parts of aqueous hydrochloric acid at 25°
C. A stream of cyanogen chloride, previously washed
with water, is bubbled through the solution which is
maintained at 25-30° C. until 3.5 parts of the gas are
absorbed. The resulting solution is sealed and allowed to
According to a further feature of the invention we pro
vide a process for the manufacture of the pyrimidine
compounds which comprises interaction of a compound
of the formula:
stand for one hour at l8-22° C. The reaction mixture
is cooled for one hour at 0° C. and is then ?ltered. The
solid residue is dissolved in 50 parts of water and the so
R2
N
R"
Rri \
51-02
lution is adjusted to pH 7 by the addition of crystalline
sodium acetate. The mixture is cooled for one hour at
60
0° C. and is then ?ltered. The solid residue is Washed
thoroughly with water, dried at 60° C. and is then crys
tallised from ethanol. There is thus obtained 2-amino
5:7-dirnethyl-s-triazolo-[2,3-c]-pyrimidine as a colourless
crystalline solid, M.P. 252° C.
wherein R1, R2 and R3 have the meaning stated above 65
Example 3
and R9 stands for a reactive substituent, and ammonia or
36 parts of 2-ethyl-4-methyl-6-hydrazino-pyrimidine are
a substance capable of generating ammonia in the re
action medium.
It is to be understood that the starting materials are
so chosen that the substituents R1, R2 and R3 are not re
placed during the process.
dissolved in 237 parts of N aqueous hydrochloric acid at
25° C. A stream of cyanogen chloride, previouslywashed
with water, is bubbled through the solution, which is main
The reactive substituent 70 tained at 25-30° C. until 16 parts of the gas are absorbed.
(R9) may be a halogen radical for example a bromine
radical and the process may be carried out by heating the
starting material with ammonia at a temperature of be
tween 100° and 250° C. and in the presence of a diluent
or solvent for example p-ethoxyethanol.
The resulting solution is sealed and allowed to stand for
one hour at 18—22° C. Excess cyanogen chloride is then
removed by evaporation under reduced pressure at 18
22° C. 100 parts of crystalline sodium acetate are then
75 added‘ and the mixture is cooled for one hour at 0° C. and
3,045,015
5
‘6
is then ?ltered. The solid residue is washed thoroughly
.
slightly and then reduced to half-volume under reduced
with water and is dried at 60° C. It is crystallised from
ethanol and there is thus obtained 2-amino-5-ethyl-7-meth
yl-s-triazolo-[2,3-c]pyrimidine as a colourless crystalline
solid, M.P. 197° C. It is characterised by having an
pressure.
The residual solution is cooled to 18-220 C. v
and, is then poured slowly into a Well stirred mixture of
1,000 parts of ice and 300 parts of v40% aqueous sodium
hydroxide solution. When the addition is complete the
infra red absorption spectrum (determined by the potas
sium bromide pressed disc technique) showing prominent
absorption bands at 3320, 3150, 2950, 1630, 1550, 11525,
mixture is stirred for one hour and is then extracted three
times using 500 parts of chloroform each time.
The."
chloroform extracts are combined and washed with 100
1500, 1430, 1350, 1320, 1206, 1170, 1118, 1032, 985, 970,
862, 844, 802, 775, 767, 751, 738 cmfl.
10 phate and ?nally evaporated at 60° C. and 24 mm. pres
The 2-ethyl-4-methyl-6-hydrazinopyrimidine used as
starting materialmay be obtained as follows: 57 parts
of 2-ethyl-4-methyl-6-chloropyrimidine are dissolved in
sure. The residual brown oil is then distilled under re
duced pressure and there isthus obtained 2-n-propyl~4
methyl-6-chloropyrimidine, as a pale yellow oil, BLP. 108
parts of ice-water, dried over anhydrous magnesium sul
160 parts of ethanol at 18—22° C. and the solution is added
110° C./24 mm.
_
dropwise to a solution of. 40 parts of hydrazine hydrate
‘
Example 5
in 160 parts of boiling ethanol. The mixture is heated
5 parts of 2-isopropyl-4-methyl-64hydrazino-py1imi~ i
under re?ux for 1151/2 hours and is then cooled at 0° C.
dine, M.P. 86° C., are dissolved in 30 parts of N aqueous
The mixture ,is ?ltered and the ?ltrate is diluted with 80
hydrochloric acid at 25° C. Astream of cyanogen chlo
parts of benzene and the mixture is evaporated to dryness.
The solid residue is boiled with 250 parts of ethyl acetate 20 ride, previously washed with water, is bubbled through
the solution, which is maintained at 25—30° C..until 2
and the suspension is ?ltered. The ?ltrate is cooled for
parts of the gas are absorbed. The resulting solution is 1
one hour at 0° C. and the mixture is then ?ltered. The
sealed and allowed to stand for one hour at 18-22° C.
solid residue is washed with cold ethyl acetate, dried at
Excess cyanogen chloride is then removed by evaporation
60° C. and is then crystallised from ethanol. There is
under reduced pressure at 18-22” C.‘ 15 parts of crystal~
thus obtained 2-ethyl-4-methyl-6-hydrazino-pyrimidine as
line sodium acetate are then ‘added and the vmixture is
a colourless crystalline solid, M.P. 150° C.
cooled for one hour at 0° C. and ‘is then ?ltered. The sol
The .2-ethyl-4-methyl-6-chloropyrimidine used as start
id residue is washed thoroughly with water and is dried ‘
ing material has a B.P. of 93° C./2‘0 mm. and may be
at 60° C. ‘It is crystallised from ethanol and there isthus
obtained according to the procedure as described at the
end of Example 4.
I
30
Example 4
obtained 2-amino-5-isopropyl-7-methyl-s-triazolo-[2,3-c]
pyrimidine, as a colourless crystalline solid, M .P. 174° C,
it'is characterised by ‘having ‘an infra-red absorption
5 parts of .2-n—propyl-4-methyl~6-hydrazinopyrimidine
spectrum (determined by the potassium bromide pressed
Washed with Water, is bubbled through the solution, which
1420, 1350, 1310, 1206, 1165, 1118, 1095, 1050, 1020,
disc technique) showing prominent absorption bands at'
are dissolved in 30 parts of N aqueoushydrochloric acid
at 25° C. A stream of cyanogen chloride, previously 35 3310, 3180,2960, 2910, 2860, 1627,1550, 1518, 15.00, '
948, 860, 850, 778, 753 cmfl. ,
'
' ~
is maintained at 25—32° C. until 2 parts of the gas are
The 2-isopropyl-4-nrethyl-6-hydrazino~pyrirnidine M.P. '
absorbed. - The resulting solution is sealed and allowed
86° C. andthe 2-isopro‘pyl-4-methyl-6#chloropyriinidine,
to stand for one hour at 18-22° C. Excess cyanogen chlo
' ride is then‘removed by evaporation under reduced pres 40 B.P. 108-110° C./24 mm. used as starting materials may
the obtained according to the, procedures described at
sure at 18—22° C. 10 parts of crystalline sodium acetate
the end of Example 4‘
\
are then added and the mixture is cooled for one hour
at 0° C. and is then ?ltered. The solid residue is washed
Example ‘6
thoroughly With water and is dried at 60° C. It is crys
5 parts of Z-phenyl-4-methyl-6~hydrazino~py1imidine,
tallised from ethanol and there is thus obtained 2—a1nino 45
M.P.
96° C., ‘are dissolved in 30 parts of 2 N ‘aqueous v
5-n—propyl-7-methyl-s-triazolo-[2,3-c] '3- pyrimidine as'a
hydrochloric acid by warrnintgto 50° C. The solution is
colourless crystalline solid, M.P. 169° C. It is charac
terised by having an infra red absorption spectrum (de
termined by the potassium, bromide pressed disc tech
nique) showing prominent absorption bands at 3320,
3180, 2950, 2910, 1650, 1630, 1550,‘ 1528, 1500, 1430,
1380, 1350, 1325, 1265, 1206, 1168, 1120, 1030, 860‘, 840,
then ‘cooled to 25 ° C., and ‘a stream of'cyanogen chloride,
previously washed with water, is bubbled through the
solution which is maintained ‘at 25—30° C. until 1.7 parts‘
50 of the ‘gas are absorbed.
800, 770, 740 cm.-1.
‘
The 2-n~propyl-4-methyl - 6-hydrazino~pyrimidine used
The resulting solution is sealed
and allowed to stand for one‘ hour at 18-220
l
Excess
cyanogen chloride is tthenremoved by evaporation under
reduced pressure at 18422“ C. 10. parts of crystalline
sodium acetate are then added and the mixture, is cooled
as starting material may be obtained as follows: 10 parts’ 55
at 0° C. and ?ltered. Thevsolid residue is washed‘ thor
oughly with water, dried at 60° C. and is cryastllised ‘from
in 13 parts of ethanol at 18—22° C. and the solution‘ is
methanol. There is thus obtained 2-‘amino-5-phenyl-7-'
added dropwise to a solution of 6.5 parts of hydrazine
of 12-n-propyl-4-methyl~6-chloropyrimidine are dissolved
hydrate in 13 parts of boiling ethanol. The mixture is
heated under re?ux for 16 hours and is then cooled at 0° 60
C. [The mixture is ?ltered and the ?ltrate is diluted with
10 parts of benzene and the mixture is evaporated to dry
methyl-s-triazolo-[2,3lc]~pyrirnidine,'as a colourless crys- _ i
tailline solid, M.P. 193° C. _
~
' Example 7
5.1 parts. of 2~methylthio-4-methyl-6-hydrazinoepyrirnie '
trees. ‘The residue is‘extracted with 100 parts of'ethyl .
dine,
M.P. 146° C., are dissolved in 30 parts of 2N laquej
acetate at 18—22° C., the suspension is ?ltered and the‘ ?l
ous hydrochloric acid ‘by gentle warming. The resulting '
trate is evaporated to dryness. The solid residue is crys
65 solution is cooled to 25 ° C. and a stream‘ of cyanogen ’
tallised from a mixture of ethyl acetate and petroleum
ether (B.P. 40—60° (3.)‘. There is thus obtained 2-n
propyl-4-methyl-6-hydrazino-pyrimidine as a colourless
crystalline solid, M.P. 87° C.
The 2-n-propyl-4-methyl-6~chloropyrimidine used as
chloride, previously washed with water, is bubbled
I
I ' _
V ‘
' -
through the solution, which is maintained at 25—30° C.‘
until 2 parts of the gas are absorbed. .The resulting mix-j ]
ture is sealed and allowed to stand for one hour at 18-22° p. i
C. and it is then cooled at 0° C. ‘and ?ltered; The solid _ 5
starting material may be obtained as follows: 88 parts of " 7.0 residue is washed thoroughly with water, dried at ‘60°. C. ‘
2-n-propyl-4-methyl~6-hydroxypyrimidine are added to
and is crystallised from 50%. aqueous ethanol. There, is‘
330 parts of phosphorus oxychloride and the mixture is
thus ‘obtained Z-amino-S~methyithio-7-rriethyl-s-triazolo#
heated gently under re?ux for 3% hours in an oil bath
[2,3-c] pyrimidine as, a colourless crystalline solid, M.P. '
heated at 150° C. The clear solution is allowed to cool 75 260° C. with decomposition.
" '
' 3,045,015
7
8
,
amino - 5 - ethoxyethyl - 7 - methyl - s - triazolo
Example 8
[2,3-c]-pyrimidine M.P. l45-147°.C. (ethanol);
5 parts of 2-ethylthio-4-methyl-6-hydrazino-pyrimidine
from 6 - hydrazino - 2-methyl-4,S-tetramethylene pyrimi
are dissolved in 30 parts of 10% aqueous acetic acid by
gentle warming. The solution is cooled to 25° C. and a
stream of cyanogen chloride, previously washed with
Water, is bubbled through the solution which is main
dine, 2-arnino-5-methyl-7,8-teatramethylene-s-triazolo
[2,3—c]-pyrimidine M.P. 211-2l2° C. (from water);
‘from 6-hydrazino-2-n-propyl-4-tri?uoromethylpyrimidine,
2 - amino - 5 - n - propyl - 7 - trifiuoromethyl - s - tri
azolo-[2,3—c]-pyrimidine M.P. 148-149° C. (light
tained at 25-30” C. until 1.8 parts of the gas are absorbed.
The resulting mixture is sealed and allowed to stand for
petroleum);
one hour at 18-22‘1 C. and it is then ?ltered. The solid 1O from 6-hydrazino-4-methyl-2-n-pentyl-pyrimidine, 2-arni~
no - 7 - methyl - 5 - n - pentyl - s - triazolo - [2,3 - c] residue is ground with 10 parts of crystalline sodium ace
tate in 100 parts of water and the mixture is then ?ltered.
pyrimidine, M.P. 151-152° C. (from ethanol);
The solid residue is washed thoroughly with water, dried
from 4-ndheptyl-6-hydrazino-2-n-propyl pyrimidine, 2
amino - 7 - n - heptyl - 5 - n - propyl - s - triazolo —
at 60° C. and is crystallised ?om ethanol. There is thus
[2,3~c]-pyrimidine, M.P. 128-l29° C. (ethanol);
obtained 2-amino-5-ethylthio-7-rnethyl-s-triazolo- [2,3-c] -
from 4-cyclohexyl-6~hydrazino-2-n-propylpyrimidine, 2
pyrimidine as a colourless crystalline solid, M.P. 210° C.
amino - 7 - cyclohexyl - 5 - n - propyl - s - triazolo -
Example 9
[2,3-c]-pyrimidine M.P. 120-122° C. (ethanol).
Example 10
10 parts of 4-chloro-6-hydrazino-2methyl-pyrimidine
The process described in Example 4 is repeated except
that 5 parts of 6-hydrazino-4-methyl-2-n—propyl pyrimi
dine are replaced by an equivalent amount of 2-n-butyl-6
are dissolved in 250 parts of ‘20% aqueous acetic acid con
hydrazino-4-methyl pyrimidine and there is thus obtained
2 - amino - 5 - n - butyl » 7 - methyl
taining 40 parts of crystalline sodium acetate. A stream
of cyanogen chloride, previously washed with water, is
bubbled through the solution which is maintained at 25
5 - triazolo - [2,3 -
c]-pyrimidine as a colourless crystalline solid M.P. 168
170° C. from ethanol.
30° C. until 4.2 parts of the gas are absorbed. The re
Similarly,
from 4-ethyl-6-hydrazino-2-methyl pyrimidine there is ob
tained 2-amino-7-ethyl-5-methyl-s-triazolo-[2,3-c1-py
rimidine M.P. 198—200° C. (from ethanol);
from 6-hydrazino-2-methyl~4-n-propyl-pyrimidine, 2-ami
sulting suspension is sealed and kept at 18-22" C. for one
hour. ‘The reaction mixture is cooled for one hour at 0°
C. and is then ?ltered. The solid residue is suspended in
30 80 parts of l N aqueous hydrochloric acid and the mix
ture is kept at 18-22° C. for 171/2 hours and then cooled
at 0° C. The solid residue is recovered, by ?ltration,
washed with ice-water, dried and crystallised from di~
met-hylformamide. There is thus obtained 2-amino-7
chloro-5-m-ethyl-s-triazolo [2,3-c]-pyrimidine as a col
no - 5 - methyl - 7 - n - propyl - s - triazolo - [2,3 - c] -
pyrimidine M.P. 182-184" C. (ethanol);
4-n-butyl-6-hydrazino-2-methyl pyrimidine, 2-amino-7-n
butyl-S-methyl-s-triazolo-[2,3-c]~pyrimidine M.P. 169°
ourless, crystalline solid M.P. 292-294° C. with decom»
C. (ethanol);
position.
2,4-diethyl-6-hydrazino-pyrimidine, Z-amino-SJ-diethyl
s — triazolo - [2,3 - c] - pyrimidine
(ethanol);
M.P.
159-160°
The process described above is repeated except that 10
parts of 4-chloro-6-hydrazino-2 methyl-pyrimidine are re
C.
_
2-ethyl-6-hydrazino-4-n-propyl-pyrimidine, 2 - amino - 5 ~
40
ethyl - 7 - n - propyl-s-triazolo-[2,3-c) -pyrimidine M.P.
placed by an equivalent amount of 4-chloro-6-hydrazino
2-n-propyl pyrimidine and there is thus obtained Z-amino
7-chloro-5-n-propyl-s_triazolo-[2,3-c1-pyrimidine as a col
162-164" C. (ethanol);
ourless crystalline solid M.P. 199-201° C. (ethanol).
6-hydrazino-2,4-di-n-propyl-pyrimidine, 2-arnino-5,7-di-n
propyl-s-triazolo- [2,3-cl -pyrimidine M.P. 158-159° C.
Example 11
(ethanol);
4-ethyl-6-hydrazino-2-n-propyl pyrimidine, 2-amino-7
2 parts of 2-amino-7-chloro-5-n-propyl-s-triazolo-[2,3
c] -pyrimidine and 5 parts of n-propylamine in 20 parts of
ethyl - 5 - n - propyl-s-triazolo-[2,3-c]-pyrimidine M .P.
ethanol are heated in a sealed tube at 150° C. for 16 hours.
l52-l53° C. (ethanol);
4-n-butyl-6-hydrazino-2-n-propyl-pyrimidine,
After cooling, the reaction-mixture is evaporated to dry
6-hydrazino-2,4,5-trimethyl~pyrimidine, 2-amino-5,7,8-tri
is recovered by ?ltration, washed with ice-water, dried and
crystallised from ethyl acetate. There is thus obtained
2-amino-7
n-butyl-S-n-propy1-s-triazolo- [ 2,3-c] ~pyrimidine M.P.
149—150° C. (ethanol);
ness under reduced pressure and the residue is treated with
excess aqueous sodium acetate solution. The solid residue
methyl-s-triazolo-[2,3-c]-pyrimidine M.P. 249-251“ C.
2 - amino - 5 - n - propyl - 7 - n - propylamino-s-triazolo
(ethanol);
[2,3-c]-pyrimidine as a colourless crystallised solid M.P.
6-hydrazino-4,5-dimethyl-2-n-propylpyrimidine, Z-amino
114-1 16 ° C.
7,8 - dimethyl - 5 - n - propyl - s - triazolo - [2,3-c]-py
rimidine, 2—amino-8-ethyl-7-methyl-5—n-propyl-s-triaz
Example 12
1 part of 2-amino-7-methyl-5-methylthio-s-triazolo
[2,3-c]-pyrirnidine and 5 parts of methylamine in 20 parts
olo~[2,3-c]-pyrimidine hemihydrate M.P. 108-110° C.
60 of dry ethanol are heated at 150° C. for 16 hours. After
rirnidine M.P. 148-l49° C. (ethanol);
5 - ethyl - 6 - hydrazine - 4 - methyl - 2 - n - propyl - py
cooling, the solution is evaporated to dryness under re
duced pressure and the residue is crystallised from etha
nol. There is thus obtained 2—amino-7-methyl-5-methyl
(ethanol);
from 6-hydrazino-Z-methyl-pyrimidine, 2-amino-5-meth
yl-s-triazolo-[2,3-c] -pyrimidine M.P. 228-230°
(ethanol);
C.
amino-s-triazolo-[2,3-c]-pyrirnidine as a colourless crys
talline solid M.P. 188° C. In a similar manner, from
from 5-allyl-6-hydrazino-4-methyl-2-n-propyl pyrimidine,
8 -allyl - Z-amino ~7-methyl-5-n--propyl-s-tri~
an equivalent amount of ethylamine there is thus ob
azolo-[2,3-c]~pyrimidine, monohydrate M.P. 85-87" C.
tained 2-arnino-5-ethylamine-7-methyl-s-triazolo-[2,3-c'l
(ethanol);
n-propylamine, 2-amino-7-methyl-5-n-propylamino-s-tri
1azolo-[2,3-c]~pyrimidine, M.P. 98-100“ C. (ether); from
dimethylarnine, 2-amino-5-dimethyl-amino-7-methyl-s-tri
pyrimidine M.P. 122-124° C. ‘(aqueous acetic acid); from
irorn 6-hydranno-4-methoxy-2,5-dimethyl pyrimidine, 2
amino - 7 - methoxy - 5,8 - dimethyl - s - triazolo - [2,3 -
ckpyrimidine M.P. 222-223 ‘’ C. (ethanol);
from 5-bromo-6-hydrazino-4-methyl-2-n-propyl pyrimi
70
azolo-[2,3-c]-pyrirnidine M.P. l33-l34° C. (ethanol).
Example 13
[2,3-c]~pyrimidine, M.P. 159-160” C. (from ethanol);
5
parts
of
6-hydrazino-4-methyl-2-methylthio-pyrimi
from 2-ethoxyethyl-6-hydrazino-4-methyl pyrimidine, 2 75
dine, 2-amin0-8-bromo-7-methyl-5.-n-propyl~s-triazolo
3,045,015
10
dine are dissolved in 24 parts of'20% aqueous acetic acid
water, is :bubbled through the solution which is maintained
containing 10 parts of crystalline sodium acetate. A
stream of cyanogen chloride, previously washed with
water, is bubbled through the solution, which is main
at 25—30° C. until 2 parts of gas are absorbed.
The reac
tion mixture is sealed and is kept at 18—22° C. for 1 hour.
The solid residue is recovered by ?ltration, washed with
Water, dried and crystallised .from ethyl acetate. ‘There is
tained at 25~30° C. until 2 parts of the gas are absorbed.
The resulting suspension is sealed and is kept for 30 min
thus obtained 2-amino-7-methyl-5-n - propyl - s - triazolo
utes at 18—22° C. and is then cooled in ice-water. The
[2,3-c]-pyrimidine, M.P. 169° C.
solid is recovered by ?ltration, washed with water, dried
Example 17
and crystallised from ethanol. There is thus obtained a
_
compound C7H9N5S, M.P. 232-234” C. with decomposi 10 The process described in Example 4 is repeated except
tion.
that 2 parts of cyanogen chloride are replaced by 3.5 parts
3 parts of the above compound (C7H9N5‘S) ‘and 11 parts
of cyanogen bromide and no attempt is made to remove
of methylamine in 20 parts of dry?-ethoxyethanol are
excess cyanogen bromide. There is thus obtained 2
heated in a sealed tube at 150° C. 1for‘16 hours. After
aamino-7-methyl-5-n-propyl-s-triazolo-[2,3-c] - pyrimidine,
cooling the resulting solution is evaporated to dryness 15 M.P. 169° C.
and the residue is crystallised ‘from ethanol. There is
thus obtained Z-amino-5-methylamino-7-methyl-s-triazolo-,
Example 18
1.6 parts of 6-hydrazino-4-methyl-2 - n - propyl - pyrim~
[2,3-c]-pyrimidine as a colourless crystalline solid, M.P.
idine, 2.1 parts of S-methyl-thiouronium sulphate and 10
188° C. (\from ethanol).
of water are heated underre?ux for 16 hours. The
The process described above is repeated except that 11 20 parts
resulting mixture is cooled in ice-water and the solid pre
parts of methylamine in 20 parts of dry ,B-ethoxyethanol
cipitate is removed by ?ltration,-washed with water, dried
are‘ replaced by an equivalent amount of dimethylamine
and crystallised from ethyl acetate. There is thus ob
in dry ethanol ‘and the sealed tube reaction is conducted
tained 2-amino-7-methyl-5-n-propyl-s-triazolo-[2,3-c]-py- ,
at 120° C.‘ There is thus obtained'2-arnino-5edimethyl
rimidine, M.P. 169° C.
amino-7-methyl-s-triazolo-[2,3-c]-pyrimidine as a colour 25
In a similar manner, in place of S-methyl thiuronium
less crystalline solid M.P. 132~~l34°v C. (ethylacetate).
sulphate, there may be used ‘equivalent amounts of S
Example'l4
methyl-N-ethyl thiuronium sulphate s-methyl-N-methyl
10 parts of 4-chloro-6-hydrazino-2-methy1-pyrimidine
thiuronium iodide or S-methyl-N,N-dimethyl vthiuronium
are dissolved in 250 parts of 20% aqueous acetic acid
sulphate, and there is likewise obtained 2-amino-7-methyl-V
30
containing 40 parts of crystalline ' sodium acetate. A
S-n-propyl-s-triazolo-[2,3-c]-pyrimidine,'M.P. 169° C.
stream of cyanogen chloride, previously washed with
'
Example 19 l
‘
water, is bubbled through the solution which is kept at
25-30° C. until 4.2 parts of gas are absorbed._ The re
An intimate mixtureof 1.66 parts of 6-hydrazino-4
sulting suspension is sealed and is kept at 18-22° C. for
methyl-2-npropyl-pyrimidine and 1 part of guanidine hy
one hour. The reaction mixture is' cooled for ‘one hour 35 drochloride is fused at 200° C. for 1%. hrs. The melt is
at 0° C; and is then ?ltered. The solid residue'is dried
allowed Ito cool to 18-22° Crand is then ?nely ground
in vacuo and there is thus obtained a compound C6H6‘N5Cl 7 and extracted with ‘boiling ethyl acetate. The ethyl ace
as a yellow crystalline solid M.P. 190~195° C. with de
tate extract is fractionally crystallised and the more
40 soluble compound recovered. There is thus obtained 2
composition.
7
'
I
2.5‘ parts of the above compound C5H6N5Cl are‘heated
amirio-Y-methyl-S-n-propy1-s-triazolo-[2,3-c] .- pyrimidine,
in a sealed tube with l4parts‘ of methylamine in 20 parts
of ethanol for 12 ‘hours at 100°" C. After cooling, the
M.P. 169° C.
'
suspension is ?ltered and the solid residue is crystallised
from n-ethanol. There'is thus obtained'Z-amino-S-meth
yl-7-methylarnino-s-triazolo-[2,3~e] - pyrimidine as a col
ourless crystalline solid M.P. 278-280” C.
v
_
>
‘
Example 20
105 parts of 4-methyl-2-n-propyl-6-(l'-semicarbazido)
45
pyrimidine and the 84 parts of phosphorus oxychloride
are heatedunder re?ux for 21/2 hours.
The bulk of the
excess phosphorus‘ oxychloride is then removed by distil
lationunder reduced pressure. The residue is'poured on
parts of m'ethylamine are replaced by an equivalent amount
to
ice and excess concentrated sodium hydroxide solution
of ethylamine. There is thus obtained 2-amino-7-ethyl 50
and the suspension so obtained'is extracted continuously
amino-S-methyl-s-triazolo-[2,3-c] -pyrimidine, M.P. 238
with ethyl acetate. The extract is dried with anhydrous
240°.C. (from n-butanol).
V
.
' The process described above is repeated except that 14
magnesium sulphate evaporated to small volume and
cooled at 0° C. The crystalline deposit is recrystallised
- Similarly, from n-propylamine, there is obtained 2
amino-5-m'ethyl-7-n-propylariiino-s-triazolo-[2,3 - c] - py
from ‘ethyl acetate and there is thus obtained 2-amino-7-w
rimidine M.P. 150-152” C. (ethanol); from dimethyl
methyl-i-n-propyl-s - triazolo - [2,3 - c] ? pyrimidine, M.P.
amine, 2-amino-7-dimethylamino - 5‘ - methyl - s - triazolo
169°
[2,3-c]-pyrimidine M.P. 239-240” C; (from methanol)
and from ammonia, 2,7-‘diamino - 5 '- methyl ,- s'é triazolo
_[,2,3-c] -pyrimidine, M.P. 292—294° C. with decomposition
(aqueous aceti'cv'acid)‘.
,' .
'
Example 15 _
“
.
‘
a
V
l
t
.
Q The 4-methyl-2-n~propyl - 6(1' - semicarbazido) pyrim
idine used as starting material may be prepared as follows:
10 parts of 6-hydrazino-4-methyl-2ln-propyl pyrimidine
60 are dissolved in 60 parts of 2 N aqueous hydrochloric acid ‘ i '
at 18~22° C. 4 parts of sodium cyanate are added and - ‘_
1 part of 2-amino-7-chloro-S-methyl-s-tiiazolo-[2,3—c]
the mixture is heated under re?ux for 30 minutes. Exit,‘
pyrimidine and 3 parts of dimethylamine in .16 parts of
cess crystalline sodium acetate is added to the hot suspen1
ethanol are heated in a sealed tube for 16 hours at 120° C.
the solid
and the
product
resulting
is recovered
mixture isbycooled
?ltration,
in ice-water,
washed with
and, ‘
The contents of the tube are cooled and the suspension is 65 sion
?ltered and the solid residue is crystallised from methanol.
ice-Water and dried. The product is crystallised from
There is thus obtained 2-amino-7-dimethy1amino-5-meth
n-‘butanol and there is thus obtained 4-methyl-2-n-propyl5. I
'yl-s-triazolo-[2,3-c]-pyrimidine as a colourless crystalline
6( I'JSemi-carbaZido) pyrimidine as a colourless crystalline ,1
solid, M.P.'239-240° C.
Example 16‘,
5' parts of 6-hydrazino-44methyl-2-n-propyl-pyrimidine
are dissolved in 20 parts of 20% aqueous acetic acid and
solid, M.P. 237-239° C. with decomposition.
70
_ 1 part of 4-methyl-2-n-propyl-6(thiosernicarbazido-l"-)a
‘ Example 21
a
. .
pyrimidine is dissolved in 20 parts of boiling 2-ethoxy- ~ ' 4
l0'parts of crystalline sodium acetate are‘added. A
ethanol. 5 parts of litharge are added and the suspension
stream of cyanogen chloride, previously washed with 75 is heated under re?ux for 25 minutes. The blackpresidiie
3,045,015
11
is removed by ?ltration and the ?ltrate is evaporated to
dryness under reduced pressure. _ The residue is extracted
with boiling ethyl acetate and the extract is treated with
charcoal, ?ltered and cooled in ice-water. The precipi
tate is recovered by ?ltration and is recrystallised from
ethyl acetate. There is thus obtained 2-amino-7-methyl
S-n-propyl-s-triazolo-[2,3-c]-pyrimidine M.P. 169° C.
12
aqueous hydrochloric acid. To this solution is added a
solution of 1.6 parts of sodium salicylate in 10 parts of
hot water. The mixture is cooled'in ice-water, ?ltered and
the solid residue is washed with ice-water and dried.
There is thus abtained 2-amino-7-methyl-5-n-propyl-s-tri
azolo-[2,3-c]-pyrimidine salicylate as a colourless crystal
line solid, M.P. 129-130" C.
The 4-methyl-2-n-propyl-6(thiosemicarbazido-1'-)py
Example 26
.
rimidine used as starting material may be prepared as fol
1.91 parts of 2-amino-7-methyl-S-n-propyl-s-triazolo
10
lows:
[2,3-c]-pyrimidine are dissolved in 10 parts of hot 1 N
5 parts of 6-hydrazino-4-methyl-2-n-propyl pyrimidine
aqueous hydrochloric acid. To this solution is added a
hydrochloride and 1.95 parts of ammonium thioeyanate
are heated under re?ux’in 110 parts of dry 2-ethoxy
ethanol for 2 hours. The solid residue is removed by
?ltration and the ?ltrate is evaporated to dryness under re
duced pressure. The residue thus obtained is warmed
with excess sodium acetate solution and then cooled in
solution of 1.99 parts of l:1'-methylenebis(2-hydroxy-3
naphthoic acid) in 11 parts of 1 N aqueous sodium hy
droxide solution. The mixture is cooled in ice~water and
the solid product is recovered by ?ltration and dried.
There is thus obtained the 2-amino-7-methyl-5-n-propyl
's-triazolo-[2,3-c]-pyrimidine salt of 1:l'-methylenebis(2
ice-water. The pale yellow solid is recovered by ?ltration,
hydroxy-Z-naphthoic acid) as a yellow solid, M.P. 280° C.
washed with water dried and crystallised from 2-ethoxy 20 with decomposition.
.
ethanol. 'There is thus obtained 4~methyl-2-n-propyl-6
Example 27
(thiosemicarbazido-1’-)pyrimidine as a colourless crystal
line solid M.P. 224° C. with decomposition.
Example 22
3.3 parts of 4 chloro-2-methyl-6(1'-semicarbazido)py
rimidine and 33 parts of phosphorus oxychloride are
heated under re?ux for 3 hours. The bulk of the excess
phosphorus oxychloride is removed by distillation under
reduced pressure and the residue is poured on to ice and
excess concentrated aqueous sodium hydroxide solution.
The cream-coloured solid is removed by ?ltration and
crystallised from 2-ethoxy-ethanol. There is thus obtained
2-arnino - 7 - chloro - 5 - methyl-s-triazolo-[2,3-c]-py
rimidine as a colourless crystalline solid M.P. 290-292“
0.5 part of 6-‘(S-ethylisothiosemicarbazido - 1' -‘ )-4~
methyl - 2 - n - propyl pyrimidine hydriodide 5 parts of
litharge and 5 parts of 2~ethoxy ethanol are heated under
re?ux for 21/2 minutes. The solid is removed by ?ltration
and the ?ltrate is evaporated to dryness under reduced
pressure and the residue is then extracted with boiling
ethyl acetate. The ethyl acetate extract is decolourised
with charcoal and the ?ltrate is cooled in ice-water. The
solid is recovered by ?ltration, washed with ethyl acetate
and dried. There is thus obtained 2-amino-7-methyl-5-n
propyl-s-triazolo-[2,3~c]-pyrimidine as a colourless crys
talline solid, M.P. 169° C.
The 6-(S-ethylisothiosemicarbazido-1’-)-4-methyl-2-n
propylpyrimidine hydriodide used as starting material may
C. with decomposition.
The 4 - chloro - 2 - methyl-6-(l’-semicarbazido)pyrimi
dine used as starting material may be prepared as follows:
be prepared as follows: 2.25 parts of 6-(thiosemicar
bazido-1'-)~4-methyl-2-n-propylpyrimidine, 40 parts of
5 parts of 4-chloro-6 hydrazino-2-methyl-pyrimidine
dry ethanol and 2 parts of ethyl iodide are heated under
are dissolved in 31.5 parts of 2 N aqueous hydrochloric 40 re?ux‘for 1 hour. The suspension gradually dissolves to
give a yellow solution which is evaporated to dryness
acid. 2.25 parts of sodium cyanate are added and the
under reduced pressure. The residual solid is dissolved
mixture is heated for 15 minutes at 95-100° C. The
in the minimum quantity of hot water and the solution
mixture is then cooled in ice-water, and the solid product
is neutralised with sodium acetate. The sticky precipitate
is recovered by ?ltration, washed with water and dried at
60° C. It is crystallised from a mixture of dimethyl ' is separated from the aqueous phase by decantation and
is triturated with ethyl acetate. There is thus obtained
formamide and ethanol. There is thus obtained 4-chloro
6-(S-ethylisothiosemicarbazido-l'-)-4-methyl-2-n - propyl
2-methyl~6(1'-semicarbazido)pyrimidine as a colourless
pyrimidine hydriodide as a pale yellow solid M.P. 180—
crystalline s'olid M.P. 240—24l° C. with decomposition.
Example 23
5 parts of 2-amino-7-methyl-5-n-propyl-s-triazolo-[2,3
c]-pyrimidine are dissolved in 13 parts of acetic acid and
20 parts of diethylether. The solution is cooled at 18-22°
C. and a stream of dry hydrogen chloride bubbled in until
precipitation is completed. The yellow solid is recovered
by ?ltration, washed with ether and crystallised from
ethanol. There is thus obtained 2-amino-7-methyl-5-n
propyl-s-triazolo-[2,3-c1-pyrimidine hydrochloride as a
pale yellow crystalline solid M.P._2l3-215° C.
Example 24
182° C. with decomposition.
Example 28
2.3 parts of 8-allyl-2-amino-7-methyl-S-n-propyl-s-tri
azolo-[2,3-c]-pyrimidine monohydrate are dissolved in 32
parts of ethanol, 0.2 part of platinum oxide is added and
the mixture is shaken in an atmosphere of hydrogen until
0.23 part of hydrogen is absorbed. The mixture is then
?ltered and the ?ltrate is evaporated to dryness under
reduced pressure and the residual solid is crystallised from
petroleum ether (B.P. 60-80° C.). There is thus ob
60 tained 2-amino-7-methyl-5,8-di-n-propyl-s - triazolo - [2,3
cJ-pyrimidine as a colourless crystal compound, M.P.
1.91 parts of 2-amino-7-methyl-5-n-propyl-s-triazolo
127-128” C.
‘
Example 29
[2,3-cl-pyrimidine are dissolved in 10 parts of hot 1 N
aqueous hydrochloric acid. 2 parts of potassium iodide
5 parts of 8-allyl-2-amino-7-methyl-5-n—propyl-s-tri
solid product is recovered by ?ltration, washed with water,
dried and crystallised from ethanol. There is thus ob
azolo-[2,3-c]-pyrimidine monohydrate are dissolved in
50 parts of acetic acid containing 25 parts of Water. 3.5
parts of bromine are added slowly with stirring at l8-22°
tained Z-amino — ~7 - methyl-5-n-propyl-s-triazolo-[2,3-c]
C.
are added and the mixture is cooled in ice-water.
The
Stirring is continued for a further 30 minutes and
pyrimidine hydriodide as a pale yellow crystalline salt
70 the mixture is then cooled at 0° C. and the solid re
M.P. 206‘208“ C. with decomposition.
moved by ?ltration, washed with ice-water, dried and
crystallised from ethanol. There is thus obtained 2
Example 25
amino-8 ( 2’,3’-dibromo-1’-n-propyl) -7-methyl-5-n- propyl
s-triazolo—[2,3-c1-pyrimidine as a colourless crystalline
1.91 parts of 2-amino-7-methy1-5-n-propyl-s-triazolo
[2,3-c1-pyrimidine are dissolved in 10 parts of hot 1 N 75 compound, M.P. 145—146° C.
3,045,015
'
13
Example 30
1.25 parts of 8-a1lyl-2-amino-7-methyl-S-n-propyl-s-tri
azolo-[2,3-c]-pyrimidine monohydrate are dissolved in
160 parts of acetone at 18-22° C. A solution of 1.4
parts of potassium permanganate in 140 parts of water
is added and the mixture is kept at 18-22" C. until the
permanganate colour disappears. The brown residue is
removed by ?ltration and the ?ltrate is evaporated to dry
ness and the residue is crystallised from acetone.
There 10
is thus obtained 2-amino-8(2’,3’-dihydroXy-l'-n-propyl—)
=0
7-methyl-5-n-propyl-s-triazolo-[2,3-c]-pyrimidine as a col
i111.
ourless crystalline solid M.P. 177-179" C.
wherein R1 is selected from the group consisting of hy
15 drogen, alkyl of up to 7 carbon atoms, hydroxyalkyl of
Example 31
up to 7 carbon atoms, allcoxyalkyl of up to 9 carbon
atoms, halogenoalkyl of up to 7 carbon atoms, allyl, cyclo
hexyl, amino, monoalkylamino of up to 3 carbon atoms,
1 part of Z-bromo-7-methyl-S-n-propyl-s-triazolo-[2,3
c]-pyrimidine M.P. 88° C. (petroleum ether, B.P. 60
dimethylamino, phenyl, methylthio and ethylthio; R2 is
80° C.) is heated with 2 parts of ammonia in 10 parts
of ,B-ethoxyethanol at 180° C. for 48 hours. After cool 20 selected from the group consisting of hydrogen, alkyl of
up to 7 carbon atoms, hydroxyalkyl of up to 7 carbon
ing the solution is evaporated to dryness under reduced
pyrimidine used as starting material may be obtained by
the action of phosphorus oxybrornide on 2-hydroxy-7-i
atoms, alkoxyalkyl of up to 9 carbon atoms, halogeno
allcyl of up to -7 carbon atoms, allyl, cyclohexyl, amino,
monoalkylamino of up to 3 carbon atoms, dimethyl
amino, methoxy and halogen; R3 is selected from the
group consisting of hydrogen, alkyl of up to 7 carbon
atoms, hydroxyalkyl of up to 7 carbon atoms, alkoxyalkyl
methyl-S-n-propyl-s-triazolo [2,3-c] ~pyrimidine which it~
of up to 9 carbon atoms, halogenoalkyl of up to 7 car
pressure and the residue is crystallised from ethylacetate.
There is thus obtained 2-amino-7-methyl-5~n-propyl-s-tri
azolo-[2,3-c]-pyrimidine, M.P. 169° C.
The 2-bromo-7-methyl-S-n-propyl-s - triazolo - [2,3-c]
self may be obtained by fusion of 6-(N-carbethoXy-N' 30 bon atoms, allyl, cyclohexyl and halogen, and the non
toxic acid-addition salts thereof.
'
hydrazino)-4-methyl-2~n-propylpyrimidine.
'
2. 2-amino-5-n-propyl - 7 - methyl-s-triazolo-[2,3-c]
pyrimidine.
Example 32
10 parts of 2-amino-7-methyl-S-n-propyl-s~triazolo
3. Z-‘amino-SJ-di - n - propyl-s-triazolo-[2,3-c]-pyrimi
dine.
35
[2,3-c]-pyrimidine, 75 parts of lactose and 22 parts of
maize starch are mixed together and granulated with 20
parts of 10% maize starch paste. The mixture is passed
4. 2~amino-5-n~propyl - 7 - n-butyl-s-triazolo-[Z?-c}
pyrimidine.
5. 2-amino-5-n-propyl - 7 - ethyl-s-triazolo-[2,3-c]py
rimidine.
'
through a 16-mesh screen, dried at a temperature not ex
6. Process for the manufacture of the pyrimidine de
ceeding 60° C. and the granules are then passed through 40 rivatives
claimed in claim I which comprises reacting a
a ZO-mesh screen. 1 part of magnesium stearate is added
member of the group consisting of pyrimidylhydrazine
and the mixture is compressed into tablets each contain
derivatives having one of the following formulae:
ing the desired weight of active ingredient. There are
thus obtained tablets suitable for therapeutic purposes.
The Z-amino-7-rnethyl-5-n-propyl - s - triazolo - [2,3-c]
45
pyrimidine used as starting material may be replaced by
an equivalent proportion of Z-amino-S:7-di-n-propyl-, 2
amino-5-n-propyl~7-n-butyl- or 2-amino-5-n-propyl-7-eth
yl-s-triazolo-[2,3-c] -pyrimidine and there are likewise ob
50 and
tained tablets suitable for therapeutic purposes.
Mono-acyl derivatives of the compounds described
‘and claimed herein are disclosed in our copending ap
plication Serial No. 16,123, ?led March 21, 1960.
What We claim is:
1. A pyrimidine derivative having a formula selected 55
from the group consisting of:
wherein R1, R2 and R3 have the meaning stated in claim
R2
60 1, and the acid-addition salts thereof, with cyanogen
halide.
|
7. Process as claimed in claim 6 wherein the cyanogen ,
halide is selected from the group consisting of cyanogen
Rik \
T“ '
chloride and bromide.
65
.
8. Process as claimed in claim 6 wherein there is, pres
ent an inert liquid medium including an acid selected I
from the group consisting of hydrochloric acid and acetic
acid.
No references cited.
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