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Патент USA US3037057

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United States Patent 0 "ice
Patented May 29, 1962
2
1
aminoalkyD-carbanilates and those of reaction (D), N
3,037,047
(methylaminoalkyl)-anilines are described in our copend
N-(CARBOXYAMINGALKYL)CARBANILATE�
William B. Wright, Jr., Woodclilf Lake, N..l., and Her
bert J. Brahander, Pearl River, N.Y., assignors to Amer
ican Cyanarnid Company, New York, N.Y., a corpora
ing application Serial No. 26,683, ?led May 4, 1960.
The compounds of the present invention are physio
5 logically active as central nervous system depressants.
For example N-[2-(carboxy-N-rnethylamino)-ethyl]-p
tion of Maine
methoxycarbanilic acid diethyl ester has muscle relaxant
N0 Drawing. Filed June 7, 1960, Ser. No. 34,356
13 Claims. (Cl. 260-471)
properties while N-[2-(N-carboxy-N~methylamino)-eth
yl]-p-chlorocarbanilic ?acid diethyl ester has tranquilizer
This invention relates to new organic compounds.
More particularly, it relates to new substituted carbanilates 10 properties. The present compounds therefore are useful
in treating various nervous disorders and, in general,
and methods of preparing the same.
where tranquilizer and muscle relaxant properties have
In the past many substituted:carbanilates have been
been found of value in the past. These compounds can
described, however, no compounds have been found
be administered in the usual pharmaceutical forms such
which have the structure indicated hereinafter.
The carbanilates of the present invention have the 15 as tablets, capsules, pills and the like. Obviously, they
can be combined with various diluents, adsorbents, ex
following general formula:
cipients and other inert ingredients in order to prepare the
(DOOR3
pharmaceutical preparation.
000R?
The following examples illustrate in detail the prepara
wherein R is a member of the group consisting of hy
0 tion of the substituted carbanilates of the present in
vention.
drogen, halogen, lower alkyl and lower alkoxy radicals,
EXAMPLE I
R1, R2 and R3 are lower alkyl radicals and n is an in
teger of 2 to 3.
Preparation of N-[2-(N-Carboxy-N-Methylamina)
?
Ethyl] ~Carbanilic Acid Diethyl Ester
The compounds of the present invention are, in gen 25
A solution of 6.3 parts of ethyl N-(2?benzylmethyl?
eral, liquids at room temperature. They are relatively
aminoethyl)~carbanilate and 2.4 parts of ethylchloro
insoluble in water ?but soluble in most organic solvents
formate inp16 parts of dry benzene is heated at re?ux for
such as, for example, alcohols, ethers, esters, ketones,
18 hours and cooled.
chloroform and the like.
The reaction mixture is shaken
The present compounds can be prepared by several 30 with dilute hydrochloric acid and the layers are separated.
The aqueous layer is extracted once with ether and the
methods which can be described as the reaction of sub
combined organic layers are washed with water, dried
stituted alkylenediamines with a lower alkyl chloro
over magnesium sulfate and distilled. The N-[Z-(N
formate. These reactions are illustrated as follows:
A.
COOIRl
benzyl
l
\N C nH in N
/
R
/
R2
I]
benzyl
OOOR3
R
\
Rt
0.
OORl
0
B.
N?CJII;?NH?
COORI
'
R
R2-?NH-?O,.H2n?N?�
/
D.
carboxy-N-methylamino)~ethyl]-carbanilic acid diethyl
R
ester, boiling point l42?l46� C./0.2 mm., is obtained in
55 66% yield.
I
EXAMPLE 11
wherein R, R1, R2, R3 and n are as de?ned above. The
illustrated reactions above may be carried out in an inert
Preparation of N-[2-(N-CarbOxy-N-Methylamina?)
solvent such as, for example, ?benzene, toluene, chloro
form and, the like. The reaction is preferably carried out
A solution of 55 parts of N-benzyl~N?-p-chlorophenyl
at a temperature within the range of 10 to 100� C. over 60
Ethyl] -p-Chlorocarbanilic Acid? Dierhyl Ester
N-methylethlenediamine and 65 parts of ethylchlorofor
a period of time ranging from 1/2 to 24 hours depending
mate in 250 parts of benzene is heated at re?ux for 18
hours and cooled. The reaction mixture is shaken with
the reaction takes place. The higher temperatures are
dilute hydrochloric acid and the layers are separated.
generally required when a benzyl group is to be replaced.
The aqueous layer is extracted with ether and the com
The starting materials in reaction (A) above, N(?benzyl 65 bined organic layers are washed with water, dried over
on the intermediate used and the temperature at which
methylaminoalkyl)-carbanilates, and also in reaction (B)
magnesium sulfate and distilled. The N-[Z-(N-carboxy
above, N - (benzylmethylaminoalkyl) - anilines, are de
N-methylamino)-ethyl]-p~chlorocarbanilic acid diethyl
scribed in our copending application Serial No. ?6,629,
ester, boiling point 158~165� C./ 0.2 mm., is obtained in
?led February 4, 1960. The starting materials of re 0 76% yield.
action (C), N-(methylaminoalkyl)~carbanilates, and re 7
EXAMPLE in
action (D), N-(methylaminoalkyl)-anilines, illustrated
above may be prepared by debenzylation of the starting
materials of reactions (A) and (B) by the use of hydro
gen and palladium carbon catalyst. Also, the prepara
Preparation of N-[2-(N-Carboxy-N-Methylamina)
Ethyl]-p-Chl0r0carbanilic Acid Dimethyl Ester
The above compound, boiling point 150-155 � C./ 0.3
tion of the starting materials in reaction (C), N-(methyl 75 mm, is obtained when methyl chloroformate is substi
3,037,047
3
ll
tuted for ethyl chloroformate in the reaction described in
mm., is obtained when N-benzyl-N'-p-bromophenyl-N?
Example II.
methylethylenediamine is substituted for N-benzyl-N'-p
chlorophenyl-N-methylethylenediamine in the procedure
EXAMPLE IV
of Example II.
Preparation of N-[2-(N-Carboxy-N-Methylamino)
Ethyl] -nz-Chl0rocarbanilic Acid Diethyl Ester
The above compound, boiling point 158-183� C./0.1
mm, is obtained in 75% yield when N-benzyl-N'-m
chlorophenyl-N~methylethylenediamine is substituted for
N - benzyl - N? - p - chlorophenyl - N - methylenediamine
in the procedure described in Example II.
EXAMPLE XI
UK
Preparation of N-[2-(N-Carboxy-N-Methylamina)
Ethyl]-m-Br0nz0carbanilic Acid Diet/1y! Ester
The above compound, boiling point 170-175" C./0.2
10 mm., is obtained when N-benzyl-N'-m-bromophenyl-N
methylethylenediamine is substituted for N-benzyl-N'~p
chlorophenyl-N-methylethylenediamine in an experiment
EXAMPLE V
such as described in Example II.
Preparation of N-[2-(N-Carboxy-N-Methy1amino)
EXAMPLE XII
Ethyl]-m-IV1ethylcarbanilic Acid Diethyl Ester
The above compound, boiling point 148?152� C./0.3
Preparation of N- [2-(Carboxy-N-Methylamino) -
Ethyl]-p-]l4etlzoxycarbanilic Acid Diethyl Ester
The above compound, boinling point 170?175� C./ 0.3
mm, is obtained when N-benzyl-N-methyl-N?-n1-tolyl
ethylenediamine is substituted for N-benzyl-N?-p-chloro
phenyl-N-methylethylenediarnine in the procedure of Ex
ample II.
mm., is obtained when N-benzyl-N?-p-methoxyphenyl
N-methylethylenediamine is substituted for N-benzyl-N?~
p-chlorophenyl-N-methylethylenediamine in the procedure
of Example II.
EXAMPLE VI
Preparation of N-[2-(N-Carboxy-N-Methylamina)
Ethyl]~m-llrlethoxycarbanilic Acid Dietlzyl Ester
The above compound, boiling point 160~165� C./0.1
We claim:
1. A compound of the formula:
mm., is obtained when N-?benzyl-N'-m-methoxyphenyl
000Rl
(300R3
N-methylethylenediamine is substituted for N-benzyl-N'
N-mcthylethylenediamine is substituted for N-benZy1-N'
p-chlorophenyl-N-methylethylenediamine in an experi
ment similar to that described in Example II.
EXAMPLE VII
wherein R is a member of the group consisting of hy
30
Preparation of N~[3-(N-Carboxy-N-Methylamin0)
Propyl] -Carbanilic Acid Dietlzyl Ester
The above compound, boiling- point 154?158� C./0.2
mm, is obtained when N-benzyl-N-methyl-N?-phenyl
drogen, halogen, lower alkyl and methoxy, R1, R2 and
R3 are lower alkyl and n is an integer of 2 to 3.
2. The compound N-[2-(N-carboxy-N-methylamino)
ethyl]carbanilic acid diethyl ester.
3. The compound N-[2-(N-carboxy-N-methylamino)
? ethyl] -p-chlorocarbanilic acid diethyl ester.
4. The compound N-[2-(N-carboxy-N-methylamino)
1,3-propanediamine is substituted for N-benzyl-N?-p
ethyl]-p-chlorocarbanilic acid dimethyl ester.
chlorophenyl-N-methylethylenediamine in a procedure
5. The compound N-[2-(N-carboxy-N~methylamino)
similar to that of Example II.
ethylJ-m-chlorocarbanilic acid diethyl ester.
40
EXAMPLE VIIII
6. The compound N-[Z-(N-carboxy-N-methylamino)
ethyl]-m-methylcarbanilic acid diethyl ester.
7. The compound N-[2-(N-carboxy-N-methylamino)
ethyl]-m-methoxy carbanilic acid diethyl ester.
8. The compound N-[3-(N-carboxy-N-methylamino
propyl]-carbanilic acid diethyl ester.
9. The compound N-[2-(N-carboxy-N~methylamino)
l-methylethyl]-carbanilic acid diethyl ester.
10. The compound N-[2-(N-carboxy-N-methylamino)
propyl]-carbanilic acid diethyl ester.
Preparation of N- [2-(N-Carboxy-N-l?tdethylamina) -
J-Methylethyl]-Carbanilic Acid Diethyl Ester
The above compound, boiling point 140?142� C./0.3
mm, is obtained when N1~benzyl-N1-methyl-N2-pheny1
l,2?propanediamine is substituted for N-benzyl-N'-p
chlorophenyl-N-methylethylenediarnine in the procedure
described in Example II.
EXAMPLE IX
Preparation of N- [Z-(N-Carboxy-N -Methylamino)
Propyl]-Carbanilic Acid Diethyl Ester
The above compound, boiling point 146-152� C./0.3
mm., is obtained in 79% yield when ethyl N-(Z-benzyi
methylaminopropyl)-carbanilate is substituted for N-(Z
50
' ethyl]~p-methoxycarba11ilic acid diethyl ester.
benzylmethylaminoethyl)-carbanilate in the process de
scribed in Example I.
EXAMPLE X
Preparation of N-[2-(N-Carboxy-N-Metlzylamin0)
11. The compound N-[2-(N-carboxy-N-methylamino)
ethyH-p-bromocarbanilic acid diethyl ester.
12. The compound N-[2-(N-carboxy-N~methylamino)
ethyl] -m-bromocarbanilic acid diethyl ester.
13. The compound N-[2-(N-carboxy-N-methylamino)
References Cited in the tile of this patent
UNITED STATES PATENTS
60
2,802,022
Groszos et a1. ________ __ Aug. 6, 1957
879,251
France ______________ __ Nov. 10, 1942
Ethyl]-p-Bram0carbanilic Acid Diethyl Ester
The above compound, ?boiling point 160-165 ?? C./0.2
FOREIGN PATENTS
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