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Патент USA US3022323

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United States PatentO?Frce
3,022,313
. Patented Feb. 20, 1962
1
2
3,022,313
ally from about 30 minutes to 7 hours, the 2-skatyl-l,3
propanediol product can be recovered by conventional
(BRGANIC C(llt/H'DUNDS
techniques, e.g., by hydrolyzing the reaction mixture with
aqueous ether followed by dilute alkali, ?ltering, and con
centrating the ?ltrate.
Jacob Szrnuszkovicz, Portage Township, Kalamazoo
County, and William C. Anthony, Kalamazoo, Mich,
assignors to The Upjohn Company, Kalamazoo, Mich.,
The novel 4-, 5-, 6-, or 7-hydroxy-substituted com
pounds can be prepared by hydrogenolysis of the corre
a corporation of Delaware
No Drawing. Filed May 11, 196i), Ser. No. 28,193
9 Claims. (Cl. ‘260—319)
sponding 4-, 5-, 6-, or 7-benzyloxy-substituted compounds.
The hydrogenolysis can be advantageously carried out in
The present invention relates to novel organic com 10 the presence of a palladium catalyst such as a palladium
black, palladium-barium sulfate, palladium-charcoal, and
pounds and more particularly relates to 2-skatyl-l,3
the like in the manner more fully disclosed in U.S.
propanediols.
The novel 2-skatyl-l,3-propanediols of the present in
Patent 2,708,197.
.
' '
The dialkyl skatylmalonates are advantageously pre
vention can be represented by the following formula:
15 pared by oondensation of a dialkyl malonate and a 3-di
a'lkylaminomethylindole represented by the formula:
20v
wherein R1, R2, and R3 represent hydrogen and alkyl con
taining l to 4 carbon atoms, inclusive, e.g., methyl, ethyl,
propyl, isopropyl, butyl, isobutyl, and the like. R4 rep
resents hydrogen, hydroxy, benzyloxy, and alkoxy con 25 wherein R2, R3, and R6 have the values given above and
taining 1 to 4 carbon atoms, inclusive, e.g., methoxy,
R7 is alkyl containing 1 to 4 carbon atoms, inclusive.
ethoxy, propoxy, isopropoxy, butoxy, and the like.
Representative dialkyl malonates which can be employed
The novel compounds of the invention show valuable
include dirnethyl malonate, diethyl malonate, diisobutyl
pharmacological activities in mammals and animals of
malonate, diethyl methylmalonate, diethyl ethylmalonate,
economic value. Illustratively, the novel compounds of 30 diethyl propylmalonate, diethyl butylrnalonate, dipropyl
the invention possess activity as central nervous system
depressants. For example, the compounds exhibit hyp
notic, anticonvulsant, tranquillizing, and drug potentiating
methylmalonate, dipropylet‘hylrnalonate, dipropyl propyl
malonate, dibutyl methylmalonate, dibutyl Vethylmalonate,
dibutyl propylmalonate, dibutyl butylmalonate, and the
activity useful in prolonging the effect of sedatives and
like. The condensation is advantageously accomplished
hypnotics in laboratory animals such as rats, mice, and 35 in the presence of an alkali such as sodium hydroxide,
the like. The novel compounds are also useful in depress
potassium hydroxide, and the like, and in the presence of
ing motor activity in such animals.
an inert solvent such as toluene, benzene, xylene, and the
In addition, the compounds of the invention exhibit
like. The reaction is generally conducted at temperatures
high absorption of radiation in the wavelength range of
between about 75° C. and about 15 0° C.; the boiling point
280-300 millimicrons and accordingly can be employed 40 of the reaction mixture is often quite convenient and
as eifective sun screens when incorporated in suitable
vehicles such as transparent film forming compositions
and oils.
The novel compounds can be combined with solid or
satisfactory.
The 3-dialkylaminomethylindoles can be prepared by
reacting an indole represented by the formula:
liquid pharmaceutical carriers and formulated as tablets, 45
powder packs, or capsules, or dissolved or suspended in
suitable solvents for oral or parenteral administration.
The novel compounds of the present invention, with the
exception of those compounds containing a hydroxy sub
stituent in the 4-, 5-, 6-, or 7-position are prepared by 50
lithium aluminum hydride reduction of dialkyl skatyl
malonates represented by the formula:
wherein R2, R3, and R5 have the values noted above, with
R. 1
a dialkylamine in the presence of formaldehyde. Prefer
ably
the dialkylamine contains from 2 to 8 carbon atoms,
55
5 4
3 CH2-—é—COOR5
inclusive. Representative dialkylamines which can be
RP;
7
2
1
R.
N/— -
boon,
employed include dirnethylamine, diethylamine, diiso
propylamine, dibutylarnine, ethylmethylamine, ethyliso
amylamine, methylheptylamine, and the like. For ex
it,
wherein R1, R2, ‘and R3 have the values noted above, R5 60 ample, the procedures disclosed by Ek et al. (J. Am.
Chem. Soc. 76, 5579, 1954), Rydon et al. (J. Chem. Soc.
represents alkyl containing 1 to 4 carbon atoms, inclusive,
2462, 1951), Bell et al. (J. Org. Chem. 13, 547, 1948) and
and R6 represents hydrogen, benzyloxy, and alkoxy con
Supniewski et al. '(Acta Polon. Pharm. 2, 125, 1938;
taining 1 to 4 carbon atoms, inclusive. The reduction is
CA. 34, 6410, 1940) can be effectively employed.
advantageously carried out in the presence of an inert
solvent such as diethyl ether, tetrahydrofuran, dibutyl 65 The starting indoles utilized for the preparation of the
3-dialkylaminomethylindoles can be prepared in the man
ether, and the like, with tetrahydro-furan generally being
ner more fully disclosed in US. Patent 2,825,734. Rep
preferred, at temperatures between about 0° C. and about
100° (3., preferably between about 15° C. and about 75°
resentative starting indoles which can be employed in
clude indole, l-methylindole, 1,2-diethylindole, l-methyl
C. In many instances it is very convenient and satisfac
tory to carry out the reduction at the boiling point of the 70 5-methoxyindole, S-benzyloxyindole, 5-ethoxyindole, Z-t
butylindole, ' 6-benzyloxyindo1e, l-propyl-G-benzyloxyin
reaction mixture, e.g., when employing tctrahydrofuran as
the inert solvent. After a suitable reaction period, usu
dole, 1,2-diethyl-S-benzyloxyindole, l-propyl-5-methoxy
3,022,313
4
3
indole, 1,2-dipropyl-5-ethoxyindo1e, 1,2-diethy1-6~benzyl~
oxyindole, 1-propyl-5-propoxyindole, 2-ethyl-6-butoxyin
EXAMPLE 2
Preparation of Z-nrethy [-2- (Z-mcthy lskatyl) -] ,3~
dole, 7-ethoxyindole, 1,2-dibutylindole, and the like.
propanedioi
The following examples are illustrative of the process
and products of the present invention, but are not to be
A. DIETHYL METHYL (2-METHYLSKATYL) MALONATE
A mixture of 25.0 g. (0.133 mole) of 2-methyl-3-di
methylaminomethylindole, 21.3 g. (0.131 mole) of di
ethyl methylmalonate, 0.4 g. of sodium hydroxide, and
construed as limiting.
EXAMPLE 1
Preparation of Z-(Z-methylskatyl)-1,3-pr0panedi0l)
300 ml. of toluene was re?uxed for 24 hours under a
10 stream of nitrogen. The mixture was cooled and ex
tracted with dilute hydrochloric acid, the extract being
discarded. The organic layer was washed with water,
dried over anhydrous potassium carbonate, ?ltered, and
A. 2-METHYL-3-DIMETHYLAMINOMETHYLINDOLE
A solution of 92.0 ml. of acetic acid and 22.2 ml. of
40% formaldehyde was cooled to 10° C. and 60.0 ml. of
concentrated. The resulting oil was crystallized from an
25% dimethylamine was added. The solution was stirred
ether-Slcellysolve B mixture, and then the solid so ob
for about 10 minutes and a solution of 39.0 g. (0.3 mole)
tained was recrystallized from a benzene-Ske1lysolve B
of Z-methylindole and 50 ml. of dioxane was added over
mixture, to yield 13.4 g. (32% of theory) of diethyl
a 1-hour period. The reaction mixture was allowed to
methyl(Z-methylskatyDmalonate which melted at 118
stand for about 16 hours at 25° C. and 600 ml. of water
120° C.
was‘then added. The mixture was extracted 3 times with 20
Anal.—Calcd. for. C1BH23NO4: C, 68.11; H, 7.30; N,
100-ml. portions of ether; the ethereal extracts were dis
4.41.
Found: C, 68.63; H, 7.42; N, 4.64.
carded. The aqueous layer was made basic with 100 g.
' B. Z-METHYL-Z-(Z-METHYLSKATYL)-1,3-PROPANEDIOL
of potassium hydroxide and the mixture was refrigerated
A solution of 12.0 g. (0.0378 mole) of diethyl methyl
at about 0° C. The resulting solid was recovered by ?l
tration and recrystallized from a mixture consisting of 25 (2-methylskatyl)malonate and 100 ml. of tetrahydrofuran
was added over a 30-minute period to a mixture of 9.1 g.
200 ml. of benzene and 750 ml. of Skellysolve B (essen
(0.24 mole) of lithium aluminum hydride and 240 ml.
tially a mixture of hexanes having a boiling range of 140
of tetrahydrofuran. The mixture was re?uxed for 4
to 160° F.), to yield 45.0 g. (79.7% of theory) of 2
hours, cooled, and decomposed with a mixture of 500
methyl-3-dimethylaminomethylindole which melted at
ml. of ether and 18 ml. of water, followed by 10 ml. of
122~124° C.
saturated aqueous sodium hydroxide solution. Themix
B. DIETHYL (2-METHYLSKATYL)MALONATE
ture was stirred for about 15‘ minutes and ?ltered.
The
?ltrate was dried over anhydrous potassium carbonate
A mixture of 18.8 g. (0.1 mole) of 2-methyl-3-dimeth
and concentrated to yield a colorless oil. The oil'
ylaminomethylindole, 15.9 g. (0.1 mole) of diethyl malo
nate, 0.2 g. of sodium hydroxide, and 300 ml. of toluene 35 solidi?ed after being washed with benzene. After re
crystallization of the solid from benzene the product,
was re?uxed for 16 hours under a stream of nitrogen.
The mixture was cooled and extracted with a solution of
2-rnethyl-2-(2-methylskatyl) - 1,3 ‘ propanediol, weighed
15‘ ml. of concentrated hydrochloric acid and 300 ml. of
water, the extract being discarded. The organic layer
7.3 g. and melted at 93-95° C.
Anal.-Calcd. for C14H19NO2: C, 72.07; H, 8.20; N,
was washed with water, dried over anhydrous sodium 40 6.05. Found: C, 71.90; H, 7.73; N, 6.07.
The ultraviolet absorption spectrum of the compound
sulfate, and ?ltered. The ?ltrate was diluted with 1500
ml. of Skellysolve B. The resulting solid, after being
recovered and dried, weighed 18.8 g. (62% of theory)
(in ethanol) exhibited maxima at 226, f 276, 282, and
290 millimicrons. The infrared absorption spectrum of
the compound (mineral oil mull) exhibited maxima at
and melted at 90° C. An 11.0 g. sample was recrystal
lized from a benzene-Skellysolve B mixture and then
from an ethanol-water mixture to yield 8.2 g. of diethyl
3380 sh, 3300, 1620, 1600 sh, 1585, 1567, 1493, 1307,
1257 sh, 1250, 1244, 1233, 1220, 1157, 1150 sh, 1130,
1064, 1050 sh, 1043, 1023, 1013, 773, 755, 748, 740 Sh,
(Z-methylskatyl)malonate which melted at 89-91" C.
683, and 677 reciprocal centimeters.
Anal.—Calcd. for C17H21NO4: C, 67.35; H, 6.98; N,
4.61. Found: C, 67.60; H, 6.98; N, 4.81.
C. 2- (2-METHYLSKATYL) -1,3-PROPANEDIOL
EXAMPLE 3
50
A solution of 8.0 g. (0.02 mole) of diethyl (Z-methyl
Preparation of Z-elhyl-Z-(1,2-diethyl-5
benzyloxyskatyl)-l,3-propaned'i0l
skatyl)malonate and 60 ml. of tetrahydrofuran was added
'
over a 30-minute period to a mixture of 6.1 g. (0.16
A. 1,Z-DIETHYL-5-BENZYLOXY-3-DIMETHYLAMINO
mole) of lithium aluminum hydride and 220 m1. of tetra 55
hydrofuran. The mixture was re?uxed for 6 hours and
In the same manner as shown in Example 1, Part A,
METHYLINDOLE
1,2-diethyl-5~benzyloxy - 3 - dimethylaminomethylindole
was then allowed to stand for 16 hours at about 25° C.
was prepared by using 1,Z-diethyl-S-benzyloxyindole
The reaction mixture was treated with 300 ml. of Wet
(U.S. Patent 2,825,734) instead of 2-methylindole.
ether, followed by 12 ml. of water and 2.4 g. of sodium
hydroxide. The mixture was made up to 700 ml. with 60
B. DIETHYL ETHYL(1,2-DIETHYL~5-BENZYLOXY
ether and ?ltered. The ?ltrate was dried over anhydrous
SKATYL) MALONATE
potassium carbonate, ?ltered, and the ?ltrate was concern
In
the
same
manner
as shown in Example 2, Part A,
trated to yield a clear oil. Crystallization from an etha
nol-water mixture yielded 3.0 g. (70% of theory) of
diethyl ethyl(1,Z-diethyl-S-benzyloxyskatyl)malonate was
2 - (2 - methylskatyl) - 1,3 - propanediol which melted at 65 prepared by using 1,2-diethyl - 5 - benzyloxy-3-dimethyl
aminomethylindole and diethyl ethylmalonate instead of
88-89° C.
Anal.—Calcd. for CHI-117N021 C, 71.20; H, 7.81; N,
6.38. Found: C, 70.62; H, 7.64; N, 6.25.
The ultraviolet absorption spectrum of the compound
(methanol) exhibited maxima at 226, f 276, 282, and 70
290,mil1imicrons. The infrared absorption spectrum of
the compound (mineral oil mull) exhibited maxima at
3380', 3300,3220 sh, 1616, 1600, 1585, 1568, 1482 sh,
1307,1232, 1120, 1070, 1040, 980, 760, and 745recip
rocal- centimeters.
2-methyl-3~dimethylaminomethylindole and diethyl meth—
lymalonate.
C. 2~ETHYL-2~ (1,2-DIETHYL-5~BENZYLQXYSKATYL) -
1,3-PROPANEDIOL
In the same manner as shown in Example 2, Part B,
2-ethyl-2-(1,2-diethyl-5~benzyloxyskatyl) - 1,3 - propane
diol was prepared by reducing diethyl ethyl(1,2-diethyl
S-benzyloxyskatyl)malonate instead of diethyl methyl
( Z-methylskatyl ) malonate.
3,022,318
6
5
EXAMPLE 4
‘EXAMPLE 7
Preparation of 2-pr0pyl-2-(1 -propyl-5-methoxy
skatyl)-1,3~pr0panedi0l
Preparation of 2-propyl-2-(1-propyl-5
A. l-PROPYL-5METHOXY-3-DIMETHYLAMINOMETHYL
A. 1-PROPYL-5~PROPOXY-3-DIMEITHYLAMINOMETHYL
’
propoxyskatyl)-.1,3-pr0panedial
INDOLE
5
INDOLE
In the same manner as shown in Example 1, Part A,
In the same manner as shown in Example 1, Part A,
l-propyl-S-methoxy - 3 - dimethylaminomethylindole was
l-propyl-S-propoxy - 3 - dimethylaminomethylindole was
prepared by using l-propyl-S-methoxyindole instead of 2
prepared by using l-propyl-S-propoxyindole instead of 2
methylindole.
'
10
B. DIETHYL PROPYL(l-PROPYL-?-METHOXYSKA'I‘YL)
,
methylindole.
‘ B. DIETHYL PROPYL(1-PROPYL-5-PROPOXYSKATYL)
MALONATE
MALONATE
In the same manner as shown in Example 2, Part A,
In the same manner as shown in Example 2, Part A,
diethyl propyl(1-propyl-5-methoxyskatyl)malonate was
prepared by using 1~propyl-S-methoxy-3~dimethy1amino
diethyl propyl(1-propyl-5-propoxyskatyl)malonate was
15
methylindole and diethyl propylmalonate instead of 2
methylindole and diethyl propylmalonate instead of 2
methyl-3-dimethylaminornethylindole and diethyl methyl
methyl-3-dimethylaminomethylindole and diethyl methyl
malonate.
C. 2-PROPYL-2‘(1-PROPYL-5-METHOXYSKATYL)-1,3
PROPANEDIOL
_
prepared by using l-propyl-5-prop0Xy-3-dimethylamino
malonate.
c. 2-PROPYL-2-(1~PROPYL-5-PROPOXYSKATYL)-1,3
20
PROPANEDIOL
In the same manner as shown in Example 2, Part B,
In the same manner as shown in Example 2, Part B,
2-propyl-2-(l-propyléS-methoxyskatyl) - 1,3 - propanediol
2-propyl-2-(1-propyl-5-propoxyskatyl) - 1,3 - propanediol
was prepared by reducing diethyl propyl(l-prop_yl-5—
methoxyskatyDmalonate instead of diethyl methyl(2~
methylskatyl) malonate.
25
was prepared by reducing diethyl propyl(1-propyl-5
propoxyskatyDmalonate instead of diethyl methy1(2—
methylskatyDmalonate.
EXAMPLE 5
EXAMPLE 8
Preparation of Z-butyl-Z-(1,2-dipr0pyl-5
Preparation of 2-ethyl~2—(2>ethyl-6
ethoxyskatyl)-1,3-propanedi0l
METHYLINDOLE
butoxyskatyl)-1,3-pr0panediol
30
A. 1,2-DIPROPYL-E-ETHOXY-S-DIMETHYLAMINO—
A. 2E'I‘HYL-6-BUTOXY-3-DIMETHYLAMINOMETHYL
>
~
In the same manner as shown in Example 1, Part A,
-1,2-dipropyl-5-ethoxy-3-dimethylaminomethylindole was
prepared by using 1,2-dipropy1-5-eth0xyindole instead of
35
2-methylindol'e.
vB. DIETHYL BUTYL('1,2-DIPROPYL-E-ETHOXYSKATYL)
In the same manner as shown in Example 2, Part A,
40
prepared by using 1,2 - dipropyl-5-ethoxy-3-dimethyl
In the same manner as shown in Example 2, Part A,
diethyl ethyl(2-ethyl-6-butoxyskatyl)malonate was pre
pared by using 2-ethyl-6-butoxy-3~dirnethylaminomethyl~v
aminomethylindole and diethyl butylmalonate instead of
2-methyl-3-dimethylaminomethylindole and diethyl meth
indole and diethyl ethylmalonate intead of 2-rnethyl-3
dirnethylaminomethylindole and diethyl methylmalonate.
ylmalonate.
C. 2-BUTYL-2-(1,2-DIPROPYL-5-ETHOXYSKATYL) -1,3
pared by using 2-ethyl-6-butoxyindole instead of Z-meth
ylindole.
B. DIETHYL ETHYL ( 2-ETHYL-6-BUTOXY SKATYL)
MALONATE
MALONATE
diethyl butyl(1,Z-dipropyl-S-ethoxyskatyl)malonate [was
INDOLE
In the same manner as shown in Example 1, Part A,
2-ethyl-6-butoxy-3-dimethylaminomethylindole was pre
45
PROPANEDIOL
c. 2-ETI-IYL-2-(Z-ETHYL-G-BUTOXYSKATYL)~1,3
PROPANEDIOL
'
In the same manner as shown in Example 2, Part C,
In the same manner as shown in Example 2, Part B,
2-ethyl-2-(2-ethyl-6-butoxyskatyl) - 1,3 - propanediol was
prepared by reducing diethyl ethyl(2-ethyl-6-butoxyskatyl)'
2-butyl-2-(1,2-dipropyl-S-ethoxyskatyl) - 1,3 - propane
diol was prepared by reducing diethyl butyl(1,2-dipropyl
malonate' instead of diethyl methyl(2-rnethylskatyl)
5-ethoxyskatyl)malonate instead of diethyl methy1(2— 50 malonate.
methylskatyl)malonate.
EXAMPLE 9
EXAMPLE 6
Preparation of Z-(I-methylskatyl)-1,3-pr0panediol
2-(1,2-diethyl-6-benzyloxyskatyl) -],3~pr0panediol
A. 1,2-DIETHYL-G-BENZYLOXY-B-DIMETHYLAMINO
55
METHYLIN DOLE
1~methyl-3-dimethylaminomethylindole was prepared by
using l-methylindole instead of 2-methylindole.
In the same manner as shown in Example 1, Part A,
'
A. l-METHYL-3-DIMETHYLAMINOMETHYLINDOLE‘
'In the same manner as shown in Example 1, Part A,
1,2-diethyl-6-benzyloxy - 3 - dimethylaminornethylindole
was prepared by using 1,Z-diethyl-6-benzyloxyindole in
60
stead‘ of Z-methylindole.
B. DIETHYL (1-METHYLSKATYL)MALONATE
In the same manner as shown in Example 1, Part B,
B. DIE'I‘HYL (1,2-DIETHYL~6~BENZYLOXYSKATYL>
diethyl (I-methyISkatyDmalOnate was prepared by using
In the same manner as shown in Example 1, Part B,
methyl-3-dimethylaminomethylindole.
1-methyl-3-dimethylaminomethylindole instead of 2
diethyl (1,2-diethyl-6-benzyloxyskatyl)malonate was pre 65
pared by using 1,2-diethylé6~benzyloxy-3-dimethylamino~
methylindole instead of 2-methyl-3-dimethylaminometh
ylindole.
2-( l-methylskatyl)-l,3-propanediol- ‘ was
'
prepared
by '
reducing diethyl (l-methylskatyDmalonate instead of di
ethyl (Z-methylskatyl)malonate.
C. 2-(1,Z-DIETHYL-G-BENZYLOXYSKATYL)-1,3
PROPANEDIOL
70
In the same manner as shown in Example 1, Part C,
12-(1,Z-diethyl-6-benzyloxyskatyl) - 1,3 - propanediol was
prepared by reducing diethyl (1,2-diethyl-6-benzyloxy
skatyl)malonate instead of diethyl (2-methylskatyl)
malonate.
C. 2-(l-METHYLSKATYL)-1,3-PROPANEDIOL
1n the ‘same manner as shown in Example 1, Part C,
"
75
EXAMPLE l0
' Preparation of 2-(1,2-diethyl'skatyl)-1,3-pr0panediol
A. 1,2-DIETHYL-3-DIMETHYLAMINOMETHYLINDOLE
In the samemanner as shown in Example 1, Partv A,
3,022,313
ducing diethyl (lethoxyskatyl)malonate instead of di
l,2-diethyl-3-dimethyl'aminomethylindole was prepared by
ethyl (Z-methylskatyl)malonate.
using 1,2-diethylindole instead of 2_-methylindole.
B. DIETHYL (LZ-DIETHYLSKATYL)MALONATE
In the same manner as shown in Example 1, Part B,
EXAMPLE 14
2- (Z-t-butylskatyl) -1,3-propanediol
diethyl (1,Z-diethylskatyl)malonate was prepared by using
1,2—diethyl-3-dimethylaminomethylindole instead of 2
A. 2-13-13UTYL-3~DIMETHYLAMINOMETHYLINDOLE
methyl-3~din1ethylaminomethylindole.
‘In the same manner as shown in Example 1, Part A,
2-t-buty1-3-dimethylaminomethylindole was prepared by
C. 2-(1,2-DIETHYLSKATYL) -1,3-PROPANEDIOL
In the same manner as shown in Example 1, i’art C, 10 using 2-t-butylindole instead of 2<methylindole.
2~(1,2-diethylskatyl)-1,3—propanediol was prepared by re
B. DIETHYL (Z-t-BUTYLSKATYL)MALONATE
ducing diethyl (1,2-diethylskatyl)malonate instead of di
In "the same manner as shown in Example 1, Part B,
ethyl (Z-methylskatyl)malonate.
diethyl (2-t-butylskatyl)malonate was prepared by using
Z-t-butyl-S-dirnethylaminornethylindole
EXAM PLE 1 1
Preparation of 2-(1~me1hyl-5~meth0xyskatyl)
1,3-pr0panedz'0l
of
2—
C. 2-(2-t-BUTYLSKATYL)-1,3-PROPANEDIOL
In the same manner as shown in Example 1,- l’art C,
2-(2-t~butylskatyl)-1,3-propanediol was prepared by re—
A. 1-METHYL-5~METHOXY-3-DIMETHYLAMINOMETHYL
ducing diethyl (Z-t-butylskatyDmalonate instead of di
INDOLE
ethyl (2-methy1skatyl)ma1onate.
In the same manner as shown in Example 1, Part A,
l-methyl - 5 - methox'yé-dimethylarninomethylindole was
EXAMPLE 15
prepared by using l-rnethyl-S-methoxyindole instead of
Z-methylindole.
instead
methyl-3-dimethylaminomethylindole.
Preparation of 2-(] ,Z-dibutylskatyl )-1 ,3-pr0parzediol
‘
B. DIETHYL (1-METHYL-5-METHOXYSKATYL)
A. 1,2-DIBUTYL-3-DIMETHYLAMINOMETHYLINDOLE
MALONATE
In the same manner as shown in Example 1, Part A,
In the same manner as shown in Example 1, Part B,
1,Z-di'butyI-3~dimethylaminomethylindole was prepared
diethyl (1-rnethyl-5-methoxyskatyl)malonate was pre
by using 1,2-dibutylindole instead of Z-methylindole.
pared by using lemethyl-s-methoxyé-dirnethylamino—
methylindole instead of 2~methyl-3-dirnethylaminomethyl
B. DIETHYL (1,2-DIBUTYLSKATYL)MALONATE
In the same manner as shown in Example 1, Part B,
indole.
diethyl (1,2-dibutylskatyl)malonate was prepared by us
ing 1,2-dibutyl-3-dimethylarninomethylindole instead of 2
C. 2- (1-METHYL-5-METHOXYSKATYL) -l,3-PROPANE
DIOL
In the same manner as shown in Example 1, Part C, 35
2—(1~rnethyl-5-meth0xyskatyl)-1,3-propauediol was pre
pared by reducing diethyl (1-methyl-S-methoxyskatyl)
malonate instead of diethyl (Z-methylskatyl)malonate.
40
EXAMPLE 12
methyl-3-dimethylaminomethylindole.
C. 2- (1,2-DIBU'1‘YLSKATYL) -1,3-PROPANEDIOL
-In the same manner as shown in Example 1, Part C,
2-(1,2-dibutylskatyl)-1,3-propanediol was prepared by re
ducing diethyl (1,Z-dibutylskatyl)malonate instead of di
ethyl (Z-methylskatyDmalonate.
Preparation of 2-(5-benzyloxyskatyl) ~1 ,3-pr0panedi0l
EXAMPLE 16
A. 5-BENZYLOXY-3-DIMETHYLAMINO1\IETHYLINDOLE
In the same manner as shown in Example 1, Part A,
A mixture of Z-(S-benzyloxyskatyl)-1,3-propanediol
(Example 12), absolute methanol, and palladium-on
S-benzyloxy-3-dimethylaminomethylindole was prepared
by using S-benzyloxyindole instead of Z-methylindole.
eharcoal catalyst was shaken under ?fty pounds hydrogen
B. 'DIETHYL (?-BENZYLOXYSKATYL)MALONATE
In the same manner as shown in Example 1, Part B,
pressure and when sufficient hydrogen was absorbed the
mixture was ?ltered.
The ?ltrate was concentrated to
d-iethyl (S-benzyloxyskatyl)malonate was prepared by us 50 dryness under reduced pressure to produce 2-(57hydroxy
ing 5-benzyloxy-3-dimethylaminornethylindole instead of
skatyl)-1,3-propanediol.
Zamethyl-B-dimethylaminomethylindole.
EXAMPLE 17 '
C. 2-(S-BENZYLOXYSKATYL);1,3—PROPANEDIOL
In the same manner as shown in Example 1, Part C,
Z-(S-benzyloxyskatyl)-1,3-propanediol was prepared by
reducing diethyl (S-benzyloxyskatyl)malonatei instead of
In the same manner as shown in Example 16, 2-ethy1
2—(1,2-diethyl-S~l1ydroxyskatyl)~1,3-propanediol was pre
pared by using 2-ethyl-2-(1,Z-diethyl-S-benzyloxyskatyl)- I
diethyl (Z-methylskatyl)rnalonate.
1,3-propanedioi (Example 3) instead of Z-(S-benzyloxy
EXAMPLE 13
60
skatyl)-l,3-propanediol.
Preparation of 2-(7-eth0xyskatyl)-l,3-pr0panedi0l
EXAMPLE 18
A. 7-ETHOXY-3-DIMETHYLAMINOMETHYLINDOLE
In the same manner as shown in Example 1, Part A,
Preparation of 2-skatyl~1,3-propanediol
7-ethoxy-3-dimethylaminomethylindole was prepared by
using 7-eth0xyindole instead of Z-methylindole.
.
A. DIETHYL SKATYLMALONATE
’
3 In thesame manner as shown in Example 1, Part B,
B. DIETHYL (7-ETHOYXYSKATYL)MALONATE
diethyl skatylmalonate was prepared by using 3-dirnethyl
aminomethylindole (gramine) instead of 2-rnethyl-3-di
In the sme manner as shown in Example 1, Part B,
diethyl (7-ethoxyskatyl)malonate was prepared by using
7-ethoxy-3-dimethylaminome-thylindole
instead
of
rnethylaminemethylindole.
2 70
methyl-3-dirnethylan1inornethylindole.
C. 2-(7-ETHOXYSKATYL)-1,3-PROPANEDIOL
In the same manner as shown in Example 1, Part C,
'
B. 2-SKATYL-1,3—PROPANEDIOL
in the same manner as shown in Example 1, Part C,
2-skatyl-1,3~propanedio1 was prepared by reducing diethyl
slratylrnalonate instead of diethyl (2-methy1skaty1)malo
2~(7-ethcxysl<atyl)-1,3-propanedi0l was prepared by re 75 nate.
Far-l
3,022,313
9
.
10
5. 2-skatyl-1,3-propanediols represented by the for
We claim:
1. Z-skatyl-l,3-propanedio1s represented by the for
mula:
>
mula:
1'31
Bi
3
CHr-Jl—OHaOH
12 R:
3
CHz-C-CHzOH
CHzOH
R:
N
is
1%,
10
wherein R1, R2, and R3 are selected from the group con
sisting of hydrogen and alkyl of 1 to 4 carbon atoms,
wherein R1, R2, and R3 are alkyl of 1 to 4 carbon atoms,
inclusive.
inclusive, and R, is selected from the group consisting of
hydrogen, benzyloxy, hydroxy, and alkoxy of 1 to 4 car
15
bon atoms, inclusive.
2. 2-skaty1-1,3-propanediols represented by the for
mula:
6. Z-skatyl-1,3-propanedi0ls represented by the for
mula:
'
3
benzyloxy12
1'11
C HrU-C H: O H
C HEOH
R2
1?Ra
wherein R1, R2, and R3 are aikyl of 1 to 4 carbon atoms,
inclusive.
8
wherein R1, R2, and R3 are alkyl of 1 to 4 carbon atoms, 25
7. Z-skatyl-l,3-propanediols represented by the for
inclusive.
mula:
3. 2-skatyl-1,3-propanediols represented by the for
rnula:
R1
3 CHr-é-CHnOH
30
RF
a
12
1
wherein R1 and R3 are alkyl of 1 to 4 carbon atoms,
inclusive.
35
inclusive, and R4 is alkoxy containing 1 to 4 carbon atoms,
mula:
40
5 4| 3 onr-c‘irn-omon
(3112011
|
wherein R3 is alkyi of 1 to 4 carbon atoms, inclusive.
8. 2-methyl-2~(Z-methylskatyl)-1,3-propanedio1.
9. 2-(2-mcthylskatyl)-1,3-propanediol.
References Cited in the ?le of this patent
Brown et al,: J. Chem, Soc., pages 3172-3176 (1952).
12 R9
N
H
wherein R1, R2, and R3 are alkyl of 1 to 4 carbon atoms,
inclusive.
4. 2-skaty1-1,3-propanediols represented by the for
67
0112011
CHaOH
R:
45
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