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Патент USA US3086039

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H; ..... ..
United States Patent 0 ”
Patented "Apr. 16, 1963
1
‘
v
2
7
prepared by a process illustrated by the following equa
3,086,030
tion:
4,4-DIALKYL AND 4,4-DIARALKYL-3BJ7B-DHIY
'
DROXY-ANDROSTANES AND DERIVATIVES
THEREOF
'
Howard]; Ringold and George Rosenkranz, Mexico City,
Mexico, aissigndrs,‘ b'y mesne assignments, to Syntax
Corporation, a corporation of Panama
‘N0 Drawing. ‘Filed June 24, 1960, Ser. No. 38,440
. Claims priority, application Mexico §ept. 7, 1959
.
27 Claims.
(Cl. 260-3975)
10
The present invention relates to novel cyclopentanophen
anthrene derivatives‘ and to a process for the production
thereof.
'
More particularly‘ the present invention relates to 4,4
dialkyL and 4,4-diaralkyl-3B,l7-?-dihydroxyandrostanes,
‘to the 19-nor compounds and to estersthereof which ‘may
also contain an alkyl substituent at ‘0-170; and a double‘
‘bond at C-5,6.
15’ V
The novel compounds of the present invention which
are hormones of the androgenic type have a high ratio 20
of anabolic to ‘androgenic activities and exhibit anti-estro—
genic, anti-androgenic and anti-gonadotrop-hic activity as
‘well as exhibit an antagonistic effect towards ~acne,iare
represented by the following formulas!
25
30
R30
35
In the’ above formulas, R represents an alkyl group . I
containing from 1 to 8 carbon atoms or an aralkyl group
containing up to 8 carbon atoms; R’ represents hydrogen
or an alkyl group containing from 1 to 8 carbon atoms;
R2 represents hydrogen or methyl; R3 and R‘1 represent
hydrogen or the acyl group of a hydrocarbon carboxylic
In the above formulas, R, R’, R2, R3 and R4 have the
same meaning as set forth previously.
In practicing the process outlined above, testosterone,
l9-nor-testosterone or- the 17a-1ower alkyl derivatives
thereof such as Hot-methyl, 17u-ethyl-, l'la-propyl-tes
tosterone or 17a-methy1-, 17a-ethy1-, 17a4propyl-19-nor
45
testosterone '(I) is added to a tertiary alcohol solution
chain, which may be substituted with groups such as hy
of potassium metal. There is then added a lower alkyl
‘droxyl, acyloxy of up to‘ 12 carbon atoms, alkoxy of up
acid containing up to 12. carbon atoms, saturated or un
saturated, of straight, branched, cyclic Tor cyclic-aliphatic
to 8 carbon atoms, amino or halogen. Typical ester
groups are the acetate, propionate, butyrate, hemisucci
nate, oaproate, aminoacetate, trimethylacetate, benzoate,
cyclopentylpropionate and , ?-chloropropionate.
The novel compounds of the present invention may be
prepared by reacting testosterone or a 17rx-lower alkyl
iodide such as ‘methyl, iodide or an aralkyl iodide such
as benzyl iodide and the mixture is stirred at room’ tem
perature for a period of time of the order of four hours
under an atomsphere of nitrogen. The reaction mixture
is then poured into water, the organic solvent is removed
by vacuum distillation and the precipitate puri?ed to give
testosterone or the corresponding 19-nor compounds with
the corresponding 4,4-di-lower alkyl or 4,4-diaralkyl-A5
an alkyl or aralkyl iodide in a tertiary alcohol in the
:androsten-l7B-ol-3-one or the 17ailower alkyl derivatives
thereof or the corresponding 19-_nor-derivatives (II).
Conventional esteri?cation of the 4,4‘-di-substituted-A5~
and-rosten-‘l7B-ol-3-ones “or their 19-nor-derivative's' give
presence of a potassium‘ tertiary ialkoxide to form the cor
responding 4,4-dialkyl or 4,4-diaralkyl derivative which
upon hydrogenation in the presence of a hydrogenation
catalyst is transformed into the corresponding 4,4-dialkyl
thevcorresponding '17~esters of hydrocarbon carboxylic
or 4,4-diaralkyl androstane derivative. Upon reduction 60 ‘acids of less than l2‘carbpon atorns (III; R’=hydrogen).
Esteri?cation of the corresponding 17oc-1OW6I’ alkyl deriva
of the 4,4-di-substituted-A5-androstene orandrostane com
pounds with a reducing agent such as sodium borohydride,
there is formed the corresponding novel 3?-hydroxy-4A
di-substituted-M-androstene or androstane compound.
The novel compounds of the present invention ‘may be
tives of 4,4-disubstituted-A5-androsten417?iol-3-ones or of
the 19-nor derivatives is effected by heating with the de
sired hydrocarbon carboxylic acid anhydride in~pyridine
solution for 24 to 48 hours at about 90° C. or by reacting
8,086,080
3
4
the steroid with the hydrocarbon carboxylic acid anhydride
corresponding 4,4 - disubstituted-androstan-l7p-ol-3-ones,
or chloride in benzene solution in the presence of p
toluenesulfonic acid. The thus formed esters of the 4,4
disubstituted-As-androsten-17,8-01-3-ones, or of the corre
sponding 19-nor-compounds, with or without an alkyl
?cation are converted into the corresponding l7-esters
19-nor and 17a-alky1 derivatives (VII), which upon esteri
(VIII). Treatment of the latter with sodium borohydride
results in the formation of the corresponding 3B-hydroxy
compounds (IX) which upon conventional esteri?cation
substituent at C-17u (III) are then treated with a reduc
ing agent such as sodium borohydride to form the corre
are converted into the 3,17-diesters (XI).
sponding 3,3-hydroxy compounds (IV) which upon con
Alternatively the 4,4-disubstituted-androstan-175-01-3
\(rent)ional esteri?cation are converted into the 3,17-diesters
ones, 19-nor or 17a-alkyl derivatives (VII) are ?rst treated
10 with sodium borohydride to form the corresponding
Alternatively, compounds of Formula II are treated
3,6,17,8-diols (X) which are then esteri?ed by conventional
with a reducing agent such as sodium borohydride to
means to form the 3,17-diesters where a secondary hy
form the corresponding 3,6,17,8-diols (V) which upon con
droxyl group is present at 0-17 (XI; R3=R‘*=acyl), or
ventional esteri?cation are transformed into 3,17-diesters
into the 3-monoesters where a tertiary hydroxyl group is
(VI) where a secondary hydroxyl group is present at 15 present at C-17 (XI; R3=acyl; R4=hydrogen).
C-17 or into 3-monoesters where a tertiary hydroxyl group
By ?rst acylating the 4,4-disubstituted-A5-androsten-17B
is present at 0-17.
ol-3-one compounds (II) by conventional means where
Another aspect of the present invention is illustrated by
a secondary hydroxyl group is present at 0-17 or by treat’
the following equation:
ment of the steroid with the acyl anhydride in benzene
20 in the presence of p-toluenesulfonic acid where a tertiary
hydroxyl group is present at O—17, there is ?rst formed
' ..._.R!
VI .
?H
R:
An”
/
‘5:
..
Acylation
the corresponding 17-esters (XII) which upon hydrogena
tion in the presence of a hydrogenation catalyst are con
l
verted into compounds of Formula VIII, which may then
be transformed into the 3?-diol compounds (IX) by treat
ment with sodium borohydride and ?nally esteri?ed to
form the 3,17-diesters (XI).
This application is a continuation-in-part of our co
XII
Bit
l Hydrogenation
l Hydrogenation
|___R.
30
pending applications Serial No. 641,038 ?led February
19, 1957, and Serial No. 702,761, ?led December 16,
1957.
The following examples serve to illustrate but are not
intended to limit the scope of the invention.
35
Example I
2 g. of potassium metal was dissolved in 100 cc. of
In
t-butanol, under an atmosphere of nitrogen. 5 g. of
testosterone was added to the solution and when it had
dissolved, there was added 6.5 cc. of methyl iodide and
the mixture was stirred at room temperature for 4 hours
under an atmosphere of nitrogen. It was then poured into
water, the organic solvent was removed by vacuum distil
lation and the precipitate was collected and washed to
Acylation
—->
i
v11
l NaBHt
neutral. Crystallization from acetone afforded 4,4-di
methyl-A5-androsten-l7?-ol-3-one with M1’. 198—201° C.,
[a]D —10° (chloroform).
__R!
One gram of 4,4-dimethyl-A5-androsten-17?-ol-3-one
was dissolved in 50 cc. of methanol and mixed with a
R2
I /
H0
g
3
R2
solution of 200 mg. of sodium borohydride in 5 cc. of
l
X
H0”
2
nit
50 water and the mixture Was kept standing for 16 hours. It
was then poured into a mixture of salt water and ice, the
excess of hydride was decomposed by the addition of a
few drops of acetic acid and the precipitate was ?ltered.
IX
Crystallization from acetone-hexane afforded 4,4-dimethyl
A5-androstene-3B,l7?-diol with M.P. 2l6—218° C., [0:]13
—82‘’ (ethanol).
This compound exhibited anti-androgenic (chick) and
1
R
A eylation\\\\I
/A cylation
\../
anti-estrogenic (mouse) activity.
OR4
60
Example II
One gram of 4,4-dimethyl-A5-androsten-l7?-ol-3-one
was added to a suspension of 300 mg. of 5% palladium on
R2
charcoal catalyst previously hydrogenated in 50 cc. of
methanol. The compound was hydrogenated at 25° C.
65 and atmospheric pressure until the equivalent of 1.1 moles
R30
I
;
XI
R/it
In the above formulas R, R’, R2, R3 and R4 have the
same meaning as stated hereinabove.
In this aspect of the invention, the 4,4-disubstituted-A5
androsten-17?-ol-3-ones, the 19-nor and 17a-alkyl de
rivatives (II) are hydrogenated in the presence of a hy
of hydrogen had been absorbed (3 hours). The catalyst
was ?ltered and the solution evaporated.
The residue
crystallized from acetone-hexane to give 4,4-dimethyl
androstan-17B-0l-3-one with M.P. 145—147° 0., [a1];
—12“ (chloroform).
In the same manner as described ‘in Example I, 1 gram
of 4,4-dimethyl-androstan-17,6-ol-3-one was treated with
sodium borohydride. After the usual work, there was
drogenation catalyst such as palladium until slightly more
formed 4,4-dimethyl-androstane-3/3,17/3-diol with M.P.
than 1 equivalent of hydrogen is absorbed to form the 75 245447“ c., [111D ~16° (ethanol).
3,086,080
' 6
Example 111
exactly the same way as described in the preceding exam
Under an atmosphere of ‘nitrogen ‘there was dissolved
2 ‘g. of potassium metal in 100 cc. of t-butanol and then
ple for 19-nor-testosterone thus giving 4,4,17a-trimethyl
19-nor-A5-androsten-17,8—ol-3-one, which upon hydrogen
ation in the manner described in such example was con
vervted 'into 4,4,17a - trimethyl-19-nor-Iandrostan-17,8-01-3
5 g‘. of l7a-methyl-testosterone; there was then added
6.5 cc. of methyl iodide and the mixture was stirred at
room temperature for 4 hours under an atmosphere of
one.
Upon treatment of 4,4,17a-trimethyl-19-nor~A5-andro
nitrogen. After pouring into water the organic solvent
sten-17B-ol-3-one and 4,4,17a-trimethy1-androstan-1713-01
was removed by distillation under reduced pressure and
the precipitate was collected by ?ltration, ‘washed to
3-one with sodium borohydride as described in the pre
ceding example, there were a?orded 4,4,17a-trimethyl-l9
neutral and puri?ed by recrystallization from acetone, 10 nor-A5-androstene
- 35,175-di0l and 4,4,17a-trimetnyl-19
thus yielding 4,4,17a-trimethyl-A5-androsten-17?-ol-3-one;
nor-androstane-3B,l75-diol.
M.P. 190—1’9‘4° C., and upon recrystallization from ace
Exam‘ple VI
tone, M.P. 194~l96° 0; [a1]; —35° (chloroform).
2 g. of the ‘above compound was added to a suspension
When in the previous examples the methyl iodide was
of 600 mg. of a 5% palladium on charcoal catalyst pre
substituted by ethyl iodide, there was obtained 4,4-diethyl
viously hydrogenated in 100 cc. of methanol and the mix
A5-androsten-l7,8-ol-3~one,
4,4-diethylJandrostan-176-01-3
ture was hydrogenated at 25° C. and atmospheric pres
one, 4,4-diethyl - A5 - androstene~3B,l7,8-diol, 4,4-'diethyl
sure, until the uptake of 1.1 molar equivalents of hydro~
gen (3 hours‘). The catalyst was removed by ?ltration
and the solution was evaporated.
androstane-3B,17,8-diol-4,4—diethyl - l7a-methyl-d5aandro
sten-I7B-ol-3-one, 4,4-diethyl - l7a~methyl-androstan-17B
20
Crystallization of the
ol-3-one, 4,4-diethyl - 17a - methyl-A5-androstene-3?,17,8
residue from acetone-hexane afforded 4,4,17a-trimethyl—
androstan-17B-ol-3—one; M.P. 183—185° C.; [a]D —-39°
(chloroform) .
diol-4,4-diethyl - 17a - metlhyl-androstane-3?,l7?-diol and
the corresponding 19-n'or~derivatives of all of the fore
going.
‘
To a solution of l g. of the above compound in 50 cc.
Example Vll
25
of methanol was added a ‘solution of 200 mg. of sodium
By substituting in the method of the preceding exam
borohydride in 5 cc. of water ‘and the mixture was kept
ples the methyl or ethyl iodide by propyl iodide there
at room temperature for 24 hours. The excess of hydride
was decomposed by the cautious addition of acetic acid
were obtained 4,4-dipropyl - A5 - androsten — l7a-ol-3-one,
4,4-dipropyl-androstan-17?-ol-3-one, 4,4-dipropyl-A5-and
and the mixture was concentrated under reduced pressure
to a small volume, and diluted with water until complete
rostene-3 {3,17,6-diol, 4,4-dipropyl - androstane-3p,17B-diol,
4,4-dipropyl-17a»methyl—A5-androsten — l7?-ol-3-one, 4,4
precipitation; the product was collected, washed with
water, dried and recrystallized from. acetone-hexane, thus
dipropylil7mmethyl-androstan-17,6-ol-3-one, 4,4-dipropyl
17a-methyl-A5-androstene - 35,17,8-diol, 4,4-dipropyl-l7a
a?fording 4,4,17a-trimethyl-androstane-3B,17,8-diol; M.P.
methyl-audiostaneé?,17,8-diol and the corresponding 19
230~234° C.; [ab -28° (ethanol).
35 nor derivatives of all of the foregoing.
In a similar manner, there was treated 1 g. of the 4,4,
17a - trimethyl - A5 - androsten - l7B-ol-3-one with sodium
Example ‘VIII
borohydride to ‘produce 4,4,l7a-trimethyl-As-androstene
‘By
substituting
in
the
method of [the preceding examples
3B,17,8-di0l;M.P.216-220° C.; [a1D —100° (ethanol).
the methyl, ethyl, or propyl iodides by benzyl iodide, there
40 were obtained 4,4-dibenzyl-A5-androsten-l7B — ol - 3 - one,
Example IV
4,4-dibenzyl-androstan-l75-01-3-one, 4,4-di'benzyl-A5 - an
2 ‘g. of potassium metal was dissolved in 100‘ cc. of
drostene-3B,17B-dio1, 4,4-dibenzyl-androstane-3B,l7?-diol,
t-buta‘nol under an atmosphere of nitrogen, 5 g. of 19-nor
4,4-dibenzyl-l7a-methyl-A5-androsten-17,6-01- 3 - one, 4,4
testosterone was added to the solution and when it had
dibenzyl-l7a-methyl-androstan7l7l8-ol-3-one, 4,4-dibenzyl
dissolved, ‘there was added 6.5 cc. of methyl iodide and
the mixture was stirred at room temperature for 4 hours 4:5 17a-methyl-A5-androstene-3B,17?-diol, 4,4-dibenzyl - 17a
under an atmosphere of nitrogen. It was then poured
into water, the organic solvent was removed by vacuum
distillation and the precipitate was collected and washed
to neutral. Crystallization from acetone afforded 4,4
dimethyl-l9-nor‘A5-androsten-175-ol-3-0ne.
methyl-androstane-BB,17B-dio1 and the corresponding v19‘
nor derivatives of all of the foregoing.
50
17a-ethyl testosterone there was obtained the 17a-ethyl
derivatives of A5-androsten-17,8-ol-3-one, of androstane
l7p-ol-3-one, o? A5-androstene-3p,17B-diol and of an
rostane-3,8,l7?-diol having two methyl, two propyl, two
One gram of 4,4-dimethyl~19-nor-A5~androsten-175-01
3-one was added to a suspension of 300 mg. of 5% pal
ladium on charcoal catalyst previously hydrogenated in
50 cc. of methanol.
The compound was hydrogenated
ethyl or two benzyl groups at C4.
at 25° C. and atmospheric pressure until the equivalent
of 1.1 niols of hydrogen had been absorbed (3 hours).
The catalyst was ?ltered and the solution evaporated.
The residue crystallized from acetone-hexane to give 4,4
dimethyl-l9-nor-androstan-17B-ol-3-one.
One gram of 4,4-dimethyl-19—nor-androstan-17?-ol-3
Example IX
iBy substituting in the method of the previous examples
Example X
By substituting the 17a-ethyl-testosterone of the pre-,
ceding example by 17a-propyl-testosterone, the corre
60 sponding Hot-propyl derivatives were obtained.
one was dissolved in 50 cc. of methanol and mixed with a
Example XI
solution of 200 mg. of sodium borohydride in 5 cc. of
By substituting the 17a-ethyl~tes0sterone and 170:
Water and the mixture was kept standing for 16 hours.
propyl-testosterone in the previous Examples IX and X by
It was then poured into a mixture of salt water and ice,
17aaethyl-l9>noratestosterone and 17a~propyl-19-nor-tes
the excess of hydride was decomposed by the addition of 65 toste‘rone, the corresponding 4,4 - dimethyl - 17a - ethyl,
a few drops of acetic acid and the precipitate was ?ltered.
4,4,l7ot-triethyl, 4,4-dipropyl-17a-ethyl, 4,4-dibenzyl-17a
Crystallization from acetone-hexane afforded 4,4-dimeth
yl-19-nor-androstane-3B,l7B-diol.
'In a similar manner, 4,4-dimethyl-19-nor-A5-androsten
17?-o1-3-one, described above, was treated with sodium 70
borohydride to produce 4,4-dimethyl-l9-nor-A5-androsten
3,3,17?-diol.
ethyl and the corresponding 17a-propy1 derivatives of 19
nor-A5-androsten-175-01-3-one, 19-nor-androstan-17? - _ol—
3-one, 19-nor-A5-androstene-3B,17B-diol and 19 — nor - an
drostane-3B,l7?-diol were obtained.
Example XII
Example V
7a-methyl-19-nor-testosterone was treated in
To a solution of 5 g. of 4,4,17a-trimethyl-A5-androsten
l7B-ol-3~one (obtained in Example III) in 30 cc. of pyri
3,086,030
O
0
dine was added 5 cc. of acetic anhydride and the solution
was heated at 90° C. for 24 hours. It was then poured
into water, heated on the steam bath for a short time,
Example I, there were formed the corresponding 17-esters
of the thus obtained 35, 17,8-diols.
Example XVIII
cooled and the precipitate was collected, thus giving the
acetate of 4,4,l7a-trimethyl-A5-androsten-17,8 - ol - 3 - one
CI
By substituting hydrocarbon carboxylic acid anhydrides
other than acetic anhydride and propionic anhydride in
the method of the preceding example, there were obtained
crystallization from acetone-hexane.
esters other than the acetates and propionates of the
1.0 g. of the latter was then hydrogenated by the method
compounds set forth therein. Among other esters, there
described in Example II to produce 4,4,17a-trimethyl
17?-acetoxy-androstan-3-one. By following the method 10 were thus prepared the caproates, benzoates and cyclo
which was washed with water, dried and puri?ed by re
described in Example I, the latter was treated with so
pentylpropionates.
dium borohydride to produce the 17-acetate of 4,4,17a
trimethyl-androstane-3B,l7l3-diol; in order to avoid the
Example XIX
1 g. of the 17-propionate of 4,4-dibenzyl-17a-ethyl
-androstane-3?,17B-diol (Example XVII) ‘in 10 cc. of
hydrolysis of the acetoxy group at C-17p, there was em
ployed as a solvent tetrahydrofuran instead of methanol
pyridine was treated with 1 cc. of acetic anhydride and
kept overnight at room temperature; it was then poured
into water, heated on the steam bath ‘for half an hour,
Example XIII
cooled and the precipitate was collected, washed with
By ?ollowing the method described in Example I, the
water and dried. Recrystallization from acetone-hexane
acetate of 4,4,17aetrimethyl-Aiandrosten-17?-ol-3-one de 20 furnished the 3-acetate-17-propi0nate of 4,4-dibenzyl-l7a
scribed in the preceding example was reduced to the ‘17
ethyl-androstane-Ii?,17,6-dio1.
and the mixture was allowed to react at room temperature
for only 8 hours.
acetate of 4,4,l7a-trimethyl-A5-androstene-B?,17,6-diol.
Example XIV
A solution of 5 g. of 4,4-dimethyl-17a-ethyl-A5-andro
sten-17/3-ol-3-one (described in Example IX) in 50 cc. of
dry benzene free of thiophene was treated with 5 cc. of
propionic anhydride in the presence of 1.5 g. of p-toluene_
sulfonic acid and kept at room temperature for 24 hours.
The benzene solution was then successively washed with
5% aqueous sodium carbonate solution, dilute hydro
chloric acid and water, dried over anhydrous sodium sul
fate and evaporated. Recrystallization of the residue
'from acetone-hexane furnished the propionate of 4,4
dimethyl-17a-ethyl-A5-androsten-17B-ol-3-one.
Example XV
of 4,4,17a-trimethyl-androsten-17?-ol-3-one (described in
Example III) in 30 cc. of pyridine and the solution was
heated at 90° C. for 24 hours. After pouring into water,
heating on the steam bath for a short period of time and
cooling, the precipitate was collected, and worked up as
described in Example XII to form the acetate of 4,4,17a
trimethyl-androstaned7/3-01-3-0ne.
Treatment of the latter compound with sodium boro- -
hydride as described in Example I afforded the acetate of
4,4,17a-ltrimethyl-androstane-3,B,17p - diol identical with
the product of Example XII.
produce the dipropionate of 4,4,17-trimethyl-A5-andro
stene-3?,17p-diol.
Example XXI
By substituting in the method of the preceding Example
the 4,4,17a-trimethyl-As-androstene-S?,17?-diol by the 4,
4,l7a-trimethyl-androstane-B?,17p-diol as well as the
propionic anhydride by acetic anhydride, there was ob
tained the diacetate of 4,4,17u-trimethyl-androstane-3?,
A mixture of 1 g. of the above compound and 50 cc. of
2% methanolic sodium hydroxide solution was kept at
room temperature vfor 4 hours, acidi?ed with acetic acid,
concentrated to a small amount under reduced pressure
and the product was precipitated by diluting with water.
The product was collected by ?ltration, washed with Water,
dried and recrystallized from acetone-hexane, thus af
fording the 17-monoacetate of 4,4,17u-trimethyl-andro
stane-3p3,l7?-diol.
Example XXII
By substituting in the preceding example propionic
anhydride for the acetic anhydride, there were formed the
Example XVI
In accordance with the method described in Example
_XIV, there was treated 1.0 g. of 4,4,l7a-trimethyl-19-nor
androstan-17?-ol-3-one in benzene in the presence of
p-toluenesulfonic acid with cyclopentylpropionic anhy~
dride instead of propionic anhydride, extending the reac
tion time to 3 days and purifying the crude product by
chromatography on neutral alumina.
zene and in the presence of p-toluenesulfonic acid, in ac
cordance with the method described in Example XII, to
l7p-diol.
5 cc. o? acetic anhydride was added to a solution of 5 g.
'
Example XX
1 g. of 4,4,l7a-trimethyl-A5-androstene-3,8,l7B-diol (Ex—
ample III) was treated with propionic anhydride in ben
There was thus ob_
tained the cyclopentylpropionate of 4,4,17a-trimethyl-l9
nor-androstan-l7B-ol-3-one.
dipropionate of 4,4,17a-trimethyl-androstame-3,9,l7?-diol.
Example XXIII
By following the methods of Examples XIX and XXI,
there were formed the 3-acetate-l7-benzoate of 4,4,17u
trimethyl-androstane-SB,17?-diol; the acetate, trimethyl~
acetate and aminoacetate of 4,4-dimethyl-17a-ethy1-A5
androsten-17?-ol-3-one and the diacetate of 4,4-dimethyl
17a-ethyl-A5-androstene-3?,17,8-diol.
Similarly the 4,4-dimethyl-17a-ethyl, 4,4,17a~triethyl,
The method o? Examples XII and XIV were applied to
4,4-dibenzyl-17a-methyl and 4,4-dibenzyl-l7a-ethyl de
rivatives of A5-androstene-3?,17;8-diol-, of androstane-313,
the 4,4,17a-trimethyl, 4,4-dimethyl-17a-ethyl, 4,4-dimeth
A5-androstene-3?,17?-diol were esteri?ed to form the di
Example XVII
yl-17a-propyl, 4,4-diethyl-17a - methyl, 4,4,17a - triethyl, 65
4,4-diethyl-17a-propy1, 4,4-dipropyl-17a-methyl, 4,4-di
pr0pyl-17a-ethyl, 4,4,l7oc - tripropyl, 4,4 - dibenzyl - 17a
methyl, 4,4-dibenzyl-17a - ethyl and 4,4 - dibenzyl - 17a
propyl derivative of A5-androsten-17?-ol-3-0ne, of andro
17B-diol, of 19-nor-androstane-3?,17,8-diol, and of 19-nor
acetates, dipropionates, dicyclopentylpropionates, 3-ace
tates-17-propionates, 3-acetates-17-cyclopentylpropionates,
3 - propionates - 17-acetates and 3-propionates-l7-cyclo
pentylpropionates.
Example XXIV
70
and of l9-nor-androstan-17?-ol-3-one obtained in the pre
By conventional reaction with acetic anhydride in pyri
vious examples and there were thus obtained the 17-ace
dine there was prepared the 17-acetates of 4,4-dimethy1
tates and l7-propionates of the foregoing compounds.
A5-androsten-l7,B-ol-3-one,
4,4-dimethylandrostan-175-01
By reduction of the thus formed 17-esters with sodium
3-one, 4,4-dimethy1-19-nor-A5-andr0sten-17?-0l-3-0ne, 4,
borohydride in accordance with the method described in 75 4-dimethyl-l9-nor-androstan-17/3-ol-3-one and of the cor
stan-l7l8-ol-3-one, of 19-nor-A5-androsten-175-01 - 3 - one
A
3,086,030
9
10
responding 4,4-diethyl, 4,4-dipropyl and 4,4-dibenzyl
compounds.
wherein R is selected from the group consisting of alkyl
and aralkyl radicals containing up to 8 carbon ‘atoms; R’
‘
I is an alkyl group containing up to 8 carbon atoms; and
In a similar conventional manner there was also pro
R2 is selected from the group consisting of hydrogen and
duced other esters such as the propionates, benzoates and
cyclopentylpropionates.
CI
Example XXV
By conventional reaction with acetic anhydride in
pyridine, there was prepared the 3,17-‘diacetate derivatives
of 4,4-dimethyl-A5-androstene-3p,17/8-diol, 4,4-dimethy1
methyl.
10. 4,4,17a-tri-lower alkyl-androstane-3?,17?-diol.
11. 4,4,l7or-trimethyl-androstane-BB,17B-diol.
12. 4,4,l7oc-tri-1OW61‘ alkyl-19‘-nor-androstane-3?,1713
diol.
O
13. A compound of the following formula:
androstane - 35,1713 - diol, 4,4 - dimethyl-19-nor-A5-andro
steneé3?,17,8-diol and of 4,4-dimethyl-19-nor-androstane
CR4
@151
35,17/3-diol.
In a similar manner there was also prepared other
esters such as the dipropionates, dibenzoates and dicyclo
pentylpropionates.
'
Example XXVI
By substituting the 4,4-diethyl, 4,4-dipropyl and 4,4
R30
dibenzyl derivatives in the methods of examples XXIV 2
and XXV, there were prepared the corresponding esters
and diestens of such 4,4-disubstituted compounds.
We claim:
1. A compound of the following formula:
0 11
R2
wherein R is selected from the group consisting of alkyl
and aralkyl radicals containing up to 8 carbon atoms; R’
is an alkyl group containing up to 8 carbon atoms; R2 is
25 selected from the group consisting of hydrogen and meth
yl; and R3 and R4 are selected from the group consisting
Ali
of hydrogen and a hydrocarbon carboxylic acyl group
of less than 12 carbon atoms and at least one of R3 and
R4 is other than hydrogen.
14. 4,4,l7a - trimethyl — androstane - 35,1713 - diola
17-acetate.
15. A compound of the following formula:
HO
OH
RR
wherein R is selected from the group consisting of alkyl
and aralkyl radicals containing up to 8 carbon atoms
and R2 is selected from the group consisting of hydroge
..
and methyl.
2. 4,4-di-lower alky1-androstane-3B,17?-diol.
3. 4,4-dimethyl-androstane-3/8,17?-diol.
asL.
/
.0 5
4. 4,4-di-lower ‘alkyl-19-nor-androstane-3/8,l7/3-diol.
5. 4,4-dimethyl-19-nor-androstane-3;8,17B-diol.
‘Bit
6. A compound of the following formula:
wherein R is selected from the group consisting of alkyl
45 and aralkyl radicals containing up to 8 carbon atoms, and
R2 is selected from the group consisting of hydrogen and
methyl.
16. 4,4-di-lower a1kyl-A5-androstene-3/8,17p-diol.
17. 4,4-dimethyl-M-androstene-35,17?-diol.
18. 4,4 - di - lower
alkyl - 19 - nor - A5 - androstene
35,17,6-diol.
19. 4,4-dimethyl-l9-nor-A5-androstene-3l3,17?-diol.
20. A compound of the following formula:
wherein R is selected from the group consisting of alkyl 55
and aralkyl radicals containing up to 8 carbon atoms;
R2 is selected from the group consisting of hydrogen and
methyl; R3 is selected from the group consisting of hydro
gen and a hydrocarbon carboxylic acyl group of less than
12 carbon atoms and R4 is a hydrocarbon carboxylic 60
acyl group of less than 12 carbon atoms.
7. 4,4-dimethyl-androstane-3,8,175-diol-diacetate.
8. 4,4 - dimethyl - 19 - nor - androstane - 35,176 - diol
diacetate.
9. A compound of the following formula:
65
wherein R is selected from the group consisting of alkyl
and aralkyl radicals containing up to 8 carbon atoms; R’
is an alkyl group containing up to 8 carbon atoms; and R2
is selected from the group consisting of hydrogen and
methyl.
21. 4,4,l7m-tri-lower alkyl-M-androstene-BB,17B-diol.
22. 4,4, 17a-trimethyl-As-androstene-3,8, 17,8-dio1.
23. 4,4,17oc - tri - lower
HO
stene-3?,17;8-diol.
75
alkyl - 19 - nor - A5 - andro
24. 4,4,l7zx-trimethyl'19~nor-A5-androstene-3/3,17/3-diol.
3,086,030
11
12
25. A compound of the following formula:
CR4
and aralkyl radicals containing up to 8 carbon atoms;
R2 is selected from the group consisting of hydrogen and
methyl; and R3 is selected from the group consisting of
hydrogen and a hydrocarbon carboxylic acyl group of
5 less than 12 carbon 1atoms; ‘and R4 is a. hydrocarbon car
R1
/
boxylic acyl grorup of less than 12 carbon atoms.
26. 4,4 - dimethyl - A5 - androstene - 33,1713 - diol
3-acetate-17-propionate.
R30
27. 4,4 - dirnethyl - 19 - nor - A5 - androstene - 313,
R/R
wherein R is selected from the group consisting of alkyl
10 17?-diol-17-acetate.
No references cited.
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