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Патент USA US3041367

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United tates Patent 0 ”
1
3,041,359
2
The novel compounds of the present invention may
therefore be illustrated by the following formulas:
\
2,2-DIALKYL ANDROGENIC TYPE HORMONES
Howard J. Ringold and Albert Bowers, Mexico City,
Mexico, assiguol's to Syntex S.A., Mexico City, Mexico,
a corporation of Mexico
\
No Drawing. Filed Aug. 29, 1058, Ser. No. 757,908
Claims priority, application Mexico Sept. 3, 1957
21 Claims. (Cl. 260-3973)
The present invention relates to cyclopentanophenan 10
threne compounds and to a process for the production
thereof.
More particularly the present invention relates to novel
androgenic type hormones which are 2,2-dialkyl deriva
tives of 19-nor-testosterone, 19-nor-dihydrotestosterone, 15
17-lower alkyl-19-nor-testosterone, l7r-lower alkyl-19-nor
dihydrotestosterone, 17 - vinyl - 19 - nor-testosterone, 17
vinyl-l9-nor-dihydrotestosterone, 17-ethinyl-19-nor-testos
terone and 17-ethinyl-19-nor-dihydrotestosterone.
The 20
present invention also relates to active hormones of the
androgenic type which are the corresponding S-hydroxy
derivatives of the aforementioned compounds. The novel
useful 19-nor androgens of the present invention show a
marked anabolic effect and practically lack androgenic
activity, they inhibit secretion of the gonadotropic by
the pituitary gland and have substantial anti-estrogenic
activity.
It has been discovered in accordance with the present
invention that treatment of 19-nor-dihydrotestosterone 30
(19-nor-androstan-17?-oIF3-one) or 17-lower alkyl or
l7-'vinyl 19-nor-dihydrotestosterone (17a-lower alkyl-l9
nor-androstan-l7?-ol~3-one or 17a-vinyl-19-nor-andro
stan-17/3-ol-3-one) with a lower alkyl iodide in the pres 35
ence of a potassium tertiary alkoxide resulted in the pro
duction of the corresponding novel 2,2-di lower‘ alkyl
‘19-ncr-androstan-17/8-ol-3-one, 2,2,17oc-tIi-l0Wer alkyl-l9
nor-androstan—l7l8-ol-3—one and 2,2-di lower alkyl-17a
vinyl-19-nor-androstan-17,8-ol-3-one. Further in accord 40
ance with the present invention it has been discovered
that monobrornination of the aforementioned compounds
gave the corresponding 4-bromo-2,2-di lower alkyl or 2,2,
17a-tri lower alkyl-19-nor-androstan-17/8-olP3-one com
pounds which on dehydrobromination gave the corre 4.5
sponding novel 2,2-di lower alkyl or 2,2,17a-t1i lower
alkyl-At-19-nor-androsten-17B-ol-3-one compounds. Fur
ther 2,2-di lower alkyl-19-nor-androstan-17p3-o1—3-one and
2,2-di lower alkyl-19-nor-A4-androsten-17?-ol-3-one were 50
converted into the corresponding Una-ethinyl compounds
by oxidation to the corresponding 17-ket0 compounds
followed by reaction with potassium butoxide and acety
lene. Partial hydrogenation of the ethinyl compounds
gave the same l7-viny1 derivatives previously mentioned
and more complete hydrogenation gave the 17a-ethyl
derivatives. All of the compounds previously mentioned
upon treatment with a reducing agent gave the corre
sponding 3-hydroxy derivatives. By conventional esteri
?cation there was also prepared the esters of these com
pounds of the nontertiary alcohol groups.
3,041,359
Patented June 26, 1962
60
3,041,359
3
r
r
4
OH
double bond between 04 and C-5 or a saturated linkage
‘
between C-4 and C-5.
-- Q = CH
The novel compounds of the present invention may be
prepared by a process illustrated in part by the follow- ‘
CTI
70
ing equations:
‘
O//\ JX
OH
OH
in-Ra
I-“Ra
1°
*1‘
Rlodlde R- I
I
—___,
0:
15
I
\
o-
,
H
H
l monobrornlnatlon
20
20 R_
OH
OH
1mm
1.03;
brginisigltlion
..
h
-
RJ
<____—
0_
Br
OH
R o5
3C0”
l
potassium
acetyllde
0H
lm-GEOH
R_R
/
0:
OH
55
l
R
K'
60
OH
/\
i
‘'
R_
O_
Q: 0
ethylene
———-—————>
I
V glycol
1'1
,,
p
R
RJ
0
[
1‘1
loxidation
65
H
erably a lower alkyl group ‘of less than 7 carbon atoms
such as methyl, ethyl and propyl. R1 represents hydro-
/\
‘
I
0
In the above formula R represents an alkyl group pref-
I
(6“ _
CZCH
‘[3’
gen or an acyl group of the type conventionally found
in an esteri?ed steroid alcohol.
These are generally 70
R
R
those derived from a hydrocarbon carboxylic acid of less
than 12 carbon atoms such as acetic, propionic, butyric,
R |
_
ggtgslsilélm
valeric, hexanoic, cyclopentylpropionic, benzoic, etc. R2
0_
ii
represents a lower alkyl group of less than 7 carbon
atoms such as methyl, ethyl or propyl. X represents a 75
:
H
hydrolysis
R
O
O
:
H
3,041,359
ard
In the above equations R and X represent the same
pounds resulting from the ?rst step just referred to are
groups as heretofore set forth. R3 represents hydrogen,
treated with slightly over 1 molar equivalent of bromine
a lower alkyl group of less than 7 carbon atoms (R2) 50 preferably in carbon tetrachloride solution to prepare the
or vinyl. R4 represents hydrogen, a lower alkyl group
corresponding 4-bromo compound and these compounds
of less than 7 carbon atoms, vinyl or ethinyl.
were dehydrobrominated with collidine. There were thus
Referring to the ?rst equation above the starting com- 7
prepared 2,2-di lower alkyl-l9Fnor-A4-androsten-1713-01
pound which may be, as illustrated, 19-nor-androstan
3-one compounds and their 17-esters or 2,2,17a-t1‘i lower
l7B-ol-3-one, or its l7rx-l0Wer alkyl or 17oz-Vinyl deriva 55 alkyl-19-nor-A4-androsten-17/3-ol-3-one compounds a 2,2
tives, in an organic solvent, preferably a tertiary lower
di lower alkyl-17u-vinyl-l9-nor-A4-androsten-l7/3-ol-3-one.
aliphatic alcohol such as t-butanol, is mixed with a po
As indicated in ‘the second equation oxidation of 2,2
tassium t-alkoxide, such as potassium t-butoxide and the
di lower alkyl-l9-nor-A4-androsten-l7B-ol-3-one com
mixture stirred under nitrogen atmosphere for a'short
pounds with preferably chromium trioxide in aqueous “I
time such as 1/2_ hour. An excess of a lower alkyl iodide
such as methyl, ethyl or propyl iodide is then added and
the reaction mixture stirred for a longer period of time
acetone gave the corresponding 2,2-di lower alkyl-19
nor-A4Fandrosten-3,l7-dione compounds. Reaction of
these last with potassium acetylide gave the correspond
i.e. of the order of 3 hours. Water is then added, the
ing Wot-ethinyl, 175-01 derivatives.
'
,
solution is neutralized with acid and the organic solvent
The ‘same type of reaction applied to 2,2-di lower
is removed by reducing pressure distillation. The residue 65 alkyl-l9-nor-androstan-l7?-ol-3-one compounds with in
is then collected by ?ltration and puri?ed to give the re
termediate protection of the 3-keto group by formation
spective 2,2-di lower alkyl, or 2,2,l7oo-tri lower alkyl or
2,2-di lower alkyl-17a vinyl derivative of l9-nor-andro
stan-17/3-ol-3-one. By conventional esteri?cation proce
of an ethylene ketal and subsequent hydrolysis of the
protective group gave the corresponding 2,2-di lower
of the type previously described there is prepared the
of the above equations.
In the fourth equation above there is illustrated the
reaction of the 17¢x-ethinyl derivatives with hydrogen to
give the l7a-vinyl derivatives and upon more complete
alkyl - 17cc - ethinyl - 19 - nor - androstan - 176 - o1 - 3
dures such as reaction with acid anhydrides or chlorides 70 one compound. This reaction is illustrated in the third
corresponding l7-acylates of hydrocarbon carboxylic
acids of less than 12 carbon atoms of the 2,2-di lower
alkyl compounds.
.
To prepare the corresponding M-compounds the com
75 hydrogenation the 17a-ethyl derivatives. Preferably the
3,041,359
7
8
partial hydrogenation was in pyridine in the presence of
dimethyl - l7a-ethinyl-3-ethylenedioxy-19-nor-androstan
a palladium on calcium carbonate catalyst and the more
1718-01.
complete hydrogenation of the ethinyl group was in di
oxane solution with a palladium on charcoal catalyst.
Without further puri?cation, the above precipitate was
dissolved in 160 cc. of acetone, mixed with 400 mg. of
p-toluenesulfonic acid and allowed to stand overnight at
Finally, in the ?fth equation above there is illustrated
room temperature. It was then poured into water and
the conversion of all of the aforementioned compounds
the precipitate was collected, dried under vacuum and
to their 3-hydroxy derivatives. In this reaction the 3
recrystallized from acetone-hexane, thus producing 2,2
keto 2,2-dimethyl derivative is treated in an organic sol
dimethyl-l7ot-ethinyl-l9-nor-androstan-l7?-ol-3-one.
vent such as aqueous dioxane with a reducing agent such
as lithium borohydride.- For the preparation of the 3 l0
Example III
esters of these compounds they were conventionally re
When in the method of Example I the 17a-methyl-l9
acted with acid anhydrides or chlorides of hydrocarbon
nor-dlhydrotestosterone was substituted by its 170:, -ethyl,
carboxylic acids of less than 12 carbon atoms preferably
-propyl or -vinyl analogue, there were obtained the 2,2
in pyridine.
The following speci?c examples serve to illustrate but 15 dimethyl derivatives of these 17tx-alkyl or vinyl substituted
are not intended to limit the present invention.
l9-nor-dihydrotestosterones.
Example IV
When in the methods of the previous examples the
A solution of 4 g. of l7u-methyl-19-nor-dihydro
methyliodide was substituted by ethyl iodide, there were
testosterone (Nat-methyl-19-nor-androstan-l75-ol-3-one) 20 obtained the corresponding 2,2-diethyl derivatives instead
in 50 cc. of ‘anhydrous t-butanol was added to a cooled
of the 2,2-dimethyl derivatives.
1
solution of potassium t-butoxide prepared by dissolving
Example V
2.2 g. of potassium in 75 cc. of anhydrous t-butanol. The
‘Example I
mixture was cooled to 0° C. and treated with 7 cc. of
methyl iodide; it was then stirred for 3 hours under an
atmosphere of nitrogen, diluted with water and the
precipitate was collected by ?ltration and puri?ed by
chromatography on a column of 200 g. of neutral
alumina, thus giving 3.4 g. of 2,2,l7a-trimethyl-l9—nor
dihydrotestosterone of M.P. 128-130° C. Recrystalliza
tion from acetone-hexane yielded the pure compound,
M.P. l40-142° C., [00]]; +102“ (chloroform).
To a solution of 750 mg. of 2,2,l7a-trimethyl-l9-nor
dihydrotestosterone, prepared as described in Example I,
in 25 cc. of dioxane there was added a solution of 500
mg. of sodium borohydride in 5 cc. of aqueous dioxane
(9:1) and the mixture was kept for 3 hours at room tem
perature. It was then acidi?ed with a few drops of acetic
acid and diluted with water. The precipitate was ?ltered
and washed with water, to give 680 mg. of 2,2,17a-tri
Example [I
methyl-l9-nor-androstan-3B,l7B-diol, M.P. 171-l73° C.,
[0L1]; +28° (chloroform).
Similarly, there was prepared 2,2-di lower alkyl
By'the method of the previous example, 19-nor-di
(methyl or ethyl) 19-nor-androstan-3B,l7?-diol from 2,2
di lower alkyl-(methyl or ethyl)-IQ-nor-dihydrostestoster
hydrotestosteroue was converted into 2,2-dimethyl-19
nor-dihydrotestosterone.
5 g, of this 2,2-dimethyl-19-nor-dihydrotestosterone
was mixed with 350 cc. of benzene, 35 cc. of ethylene
glycol and 250 mg. of p-toluenesulfonic acid and the mix
ture was boiled under re?ux for 48 hours with the use of
an adapter for the continuous removal of the water
formed during the reaction.
100 cc. of 2 normal sodium
vcarbonate solution ‘and 100 cc. of water were added to the 45
cooled mixture and the benzene layer was separated,
washed with water and evaporated to dryness. Recrystal
lization from acetone-hexane afforded 2,2-dimethyl-3
one, as well as well as the corresponding 2,2-di lower
alkyl-17a-methyl, ethyl, propyl, vinyl or ethinyl-19-nor
androstan-3?,l7B-diols from the corresponding 17a
methyl, ethyl, propyl, vinyl or ethinyl-substituted 2,2-di
' alkyl-l9-nor-dihydrotestosterone.
Example VI
A solution of l g, of 2,2-dimethyl-19-nor-dihydro
testosterone in 20 cc. of carbon tetrachloride was mixed
with a few drops of a saturated solution of hydrogen
bromide in carbon tetrachloride, followed by the addition
of 0.6 g. of bromine in 5 cc. of carbon tetrachloride, with
A suspension of'3 g. of chromium trioxide in 25 cc. of 50 stirring, and in the course of approximately 5 minutes,
while the temperature of the mixture was maintained
pyridine was added to a solution of 3 g, of the above ketal
in 20 cc. of anhydrous Pyridine. The suspension was
below 18° C.; it was then kept for 1 hour at room tem
ethylenedioxy-19-nor-androstan-17B-ol.
prepared by adding the powdered chromium trioxide
in 4 portions to the pyridine, maintaining the temperature
perature, diluted with water, mixed with 100 cc. of ether
and the organic layer was separated, washed with water,
below 35° C., until the dark red color characteristic of 55 dried over anhydrous sodium sulfate and evaporated to
dryness under reduced pressure. The residue consisted
chromium trioxide disappeared. The mixture of the
of the crude 4 - bromo - 2,2 - dimethyl-l9-nor-dihydro
steroid solution and the oxidizing reagent was kept for 24
testosterone.
~
hours at room temperature, diluted with ethyl acetate
The above bromo compound was mixed with 5 cc. of
and ?ltered through celite; the solution was washed with
water until the washings were coloreless, dried over anhy 60 collidiue and the mixture was boiled under re?ux for 1
drous sodium sulfate and evaporated to dryness under
hour. It was poured into dilute sulfuric acid and ice
and the precipitate was extracted with ether. The ether
reduced pressure. There was thus obtained 2,2-dimethyl
3-ethylene-dioxy-19-nor-audrostan-l7-one.
solution was washed with dilute sulfuric acid and water,
dried over anhydrous sodium sulfate and evaporated to
2 g. of 2,2-dimethyl-3-ethylenedioxy-19-nor-androstan
l7-one was dissolved in 80 cc. of anhydrous benzene 65 dryness. The residue was puri?ed by chromatography
and added under nitrogen to a cooled solution of potas
in a column of ‘alumina, thus a?ording the pure 2,2-di
sium t-butoxide prepared by dissolving 2 g. of potassium
methyl-l9-nor-testosterone.
Similarly, there were prepared the corresponding 2,2
dimethyl-l7a-rnethyl or ethyl-19-nor-testosterones from
phere of nitrogen. The stream of nitrogen was substituted
by a slow stream of dried purified acetylene and this 70 the corresponding l7a-ethyl or methyl substituted 2,2
metal in 100 cc. of anhydrous t-butanol, under ‘an atmos
stream was allowed to pass through the solution for 40
hours. The mixture was then poured into 400 cc. of
dilute hydrochloric acid, the organic solvents were re
moved by steam ‘distillation, the residue was cooled and
the precipitate was ?ltered; there was thus obtained 2,2 75
dimethyl-19-nor-dihydrotestosterones.
The 2,2-diethyl
lQ-nor-dihydrotestosterones, with or without a methyl or
ethyl substitutent at C-17a in a similar manner gave 2,2
diethyl-l9-nor-testosterone or 2,2-diethyl-17m-methyl or
ethyl-19-nor—testosterones, respectively.
3,041,359
9
l0
,
Example XI
By the method of Example X, 2,2-dimethyl-17a-ethinyl
Example VII
In other experiments the bromination of Example VI
19-nor-testosterone was hydrogenated until the equivalent
was carried out in glacial acetic acid instead of carbon
tetrachloride, with the same ?nal result.
of 2 mols of hydrogen was absorbed.
There was thus
obtained 2,2—dimethyl-17a-ethyl-19-nor-testosterone, iden
Example VIII
tical to the one obtained in accordance with the previous
example.
An oxidizing solution was prepared by mixing 26 g. of
chromium trioxide with 23 cc. of concentrated sulfuric
acid and diluting with water to a total volume of 100 cc.
1 g. of 2,2-dimethyl-19-nor-testosterone, obtained by
any of the methods of Examples VI and VII, was dis
Example XII
'10
When in the method of Example VIIl 2,2-dimethyl-19
nor-testosterone was substituted by 2,2-diethyl-19-nor
testosterone; there was obtained as an intermediate 2,2-kdi
ethyl-19-nor-A4-androsten-3,17-dione and as ?nal product
solved in 120 cc. of acetone and cooled to 10—,15° C. in
an ice bath. There was then added 1.6 cc. of the oxi
2,2-diethyl-17a-ethinyl-19-noratestosterone, which was in
dizing solution, with stirring, in the course of 5 minutes, 15 turn hydrogenated to 2,2-diethyl-l9-nor-17a-vinyl~testos
terone, in accordance withthe method of Example IX.
while the temperature was kept below 15° C. After 2
more minutes the mixture was diluted with water to ‘a
Example XIII
volume of approximately 500 cc. and the white precipitate
formed was ?ltered, well washed with water, dried under
vacuum and recrystallized from acetone-hexane. There
was thus obtained 2,2-dimethyl-A4-19-nor-androsten-3,17
dione.
A solution of potassium t-butoxide was prepared by
dissolving 1 g. of potassium metal in 14 cc. of t-butanol,
A mixture of 1 g. of 2,2-dimethyl-19-nor—testosterone,
10 cc. of pyridine and 1 cc. of acetic anhydride was kept
overnight at room temperature, poured into water ‘and .
heated on the steam bath for ‘half an hour. The mixture
was cooled and the precipitate was collected, washed,
dried and recrystallized from acetone-hexane. There was
the solution was cooled and the ‘air in the apparatus was 25 thus obtained 2,2-dimethyl-l9~nor~testosterone acetate.
substituted by nitrogen. To this solution there was ‘added
Example XIV
‘a solution of 1 g. of 2,2-dimethyl-l9-nor-n4eandrosten-3,
By the same conventional method of Example Xlli,
there was esteri?ed the secondary hydroxyl groups of all
of the 2,2-dimethyl-‘androstanes described; instead of an
17-dione in 10 cc. of toluene, with stirring under nitrogen
and in the course of 2 minutes. The stirring under nitro
gen was continued for a further half hour, when a
acid vanhydride there, can also be used the acid chloride.
homogeneous brown solution was obtained. The nitro
The ‘anhydride or chloride were those derived from a
gen was then substituted for a slow stream of dried
hydrocarbon carboxylic acid of to 12 ‘carbon atoms.
puri?ed acetylene which was allowed to pass for 16
There was thus prepared 1a great variety of esters, and
hours, at room temperature with stirring. The mixture
was acidi?ed with dilute hydrochloric'acid to Congo red 35 more speci?cally, C—17 acetates, prop-ionates, cyclopentyl
propionates and benzoates of 2,2-methyl or ethyl-19-nor
paper ‘and the reaction product was extracted with toluene.
testosterone and 2,2-dialkyl-19-nor-dihydrotestosterone,
The toluene was washed with water to neutral, dried over
thesame C—3 esters of the Not-substituted 2,2-dia1kyl-l9
anhydrous sodium sulfate, ?ltered ‘and concentrated under
vacuum to approximately 15 cc.
nor-androstan-3?,17,6-diols previously described, as well
It was then passed
through a short column of alumina, washing the column 40 as C—3,17 idiesters of these diols without substituent at
‘Cl-17a.
with ‘a little toluene. Evaporation of the solution under
We claim:
'
reduced pressure afforded 2,2-dimethyl-17a-eminyl-19—
l. 2,2,17a-trimethy1-19-nor-A4-androsten-17,8-01-3-one.
2. A compound of the following formula:
nor-testosterone, which was puri?ed by recrystallization
from acetone-hexane.
Example IX
45
0
ll
A suspension of 300 mg. of 2% palladium on calcium
carbonate in 30 cc. of pure pyridine was pre-hydrogenated
at room temperature for 3 hours. There was then added
1 g. of 2,2-dimethyl-17a-ethinyl-19-nor-testosterone, pre 50
pared as described in Example VIII, and the mixture was
stirred under hydrogen at room temperature until the
equivalent of 1 mol of hydrogen had been absorbed. The
catalyst was removed by ?ltration and washed with a
little pyridine and the combined ?ltrate and washings was 55
wherein R is a lower alkyl group and both R’s are the
evaporated to dryness under vacuum. The residue was
same and X is selected from the group consisting of a dou
dissolved in ether, washed with dilute hydrochloric acid,
ble bond between C—4 and C—5 and a saturated linkage
water, 5% sodium carbonate solution and again with
between C—4 and C—5.
water to neutral. Recrystallization of the residue from
3. 2,2-dimethyl-19-nor~A4-androsten-3,17-dione.
4. A compound of the following formula:
acetone-hexane yielded 2,2-dimethyl-17a-vinyl-l9-n0r
testosterone.
Example X
A solution of 1 g. of 2,2-dimethyl-17a-vinyl-19-nor 65
testosterone, obtained as described in Example IX, in 75
cc. of dioxane was mixed with 0.4 g. of previously re
duced 5% palladium on charcoal catalyst and the mix
ture was hydrogenated ‘at room temperature with stirring
until the equivalent of one mol of hydrogen was ‘absorbed.
It was then ?ltered through celite, washing the ?lter with
dioxane, and the combined ?ltrate and washings was
evaporated to dryness under reduced pressure. The resi
, due ‘crystallized from acetone-hexane to give 2,2-dimethyl
Not-ethyl-1-9-nor-testosterone.
wherein R is a lower alkyl group and both R’s are the
75 same and X is selected from the group consisting of a dou
3,041,359
12
ble bond between (3-4 and C-5 and a saturated linkage
between C-4 and C-5.
5. 2,2-dirnethy1 - 17oz - vinyl-19-nor-androstan-1718-01
3-one.
6. 2,2,-climethyl - 17a - vinyl-l9-nor-A4-androsten-17,8
ol-3-one.
7. A compound of the following formula:
'
‘
wherein R is a lower alkyl group and both R’s are the
same, R2 is a lower alkyl group, X is selected from the
group consisting of a double bond between 0-4 and C—5
and a saturated linkage between C-4 and C-5 and R1 is
5 selected from the group consisting of hydrogen and a hy
drocarbon carboxylic acyl group of less than 12 carbon
atoms.
16. 2,2,17a-trimethyl - 19 - nor - androstan - 35,1713
on
diol.
“wQECLH
17. The 3-hydrocarbon carboxylic esters of less than
12 carbon atoms of 2,2,17a-trlmethyl-19-nor-androstan—
’
35,17?-diol.
18. A compound of the following formula:
15
J.
wherein R is ‘a lower alkyl group and both R’s are the
same and X is selected from the group consisting of a dou
ble bond between C-4 and C-5 and a saturated linkage
between C54 and C-5.
8. 2,2-dirnethyl - 17a - ethinyl-l9-nor-androstan-17/3-ol
3-one.
25
e10
9. 2,2-dlmethy1 - 17oz - ethinyl-l9-nor-A4-androsten-1718
ol—3-one.
wherein R is a lower alkyl group and both R’s are the
same, X is selected from the group consisting of a double
bond between 0-4 and C-5 and a saturated linkage be
tween C-4 and C-5 and R1 is selected from the group
10. A compound of the following formula:
consisting of hydrogen and a hydrocarbon carboxylic
acyl group of less than 12 carbon atoms.
19. 2,2-dimethyl - 17a - vinyl-19-nor-androstan-3,B,17;3
diol.
20. A compound of the following formula:
35
OH
@‘0
wherein R is a lower alkyl group and both R’s are the
same, X is selected from the group consisting of a dou
ble bond between 0-4 and C—5 and a saturated linkage
between C—4 and C-5 and R1 is selected from the group
consisting of hydrogen and a hydrocarbon carboxylic acyl
group of less than 12 carbon atoms.
45
1 1. 2,2-dimethyl-19-nor-androstan-3?,1718-diol.
12. The hydrocarbon carboxylic esters of less than 12
carbon atoms of 2,2-dimethyl-19-nor—androstan—313,175
diol.
wherein R is a lower alkyl group and both R’s are the
same, X is selected from the group consisting of a double
bond between 0-4 and C-5 and a saturated linkage be
tween C-4 and C-5 and R1 is selected from the group
13. 2,2Pdimethyl-l9-uor-A4-androsten~3;3,17,8-diol.
14. The hydrocarbon carboxylic esters of less than 12
carbon atoms of 2,2-dirnethyl-19-nor-A4-androsten-3/3,17,8
diol.
consisting of hydrogen and a hydrocarbon carboxylic acyl
group of less than 12 carbon atoms.
.
21. 2,2-climethyl - 17a - ethinyl - l9 - nor-androstan
15. A compound of the following formula:
35,1713-(11‘01.
References Cited in the ?le of this patent
UNITED STATES PATENTS
2,813,880
2,845,381
2,852,537
65
Campbell et al. ______ .._ Nov. 19, 1957
Tindall ______________ __ July 29, 1958
Ringold et al. ________ __ Sept. 16, 1958
OTHER REFERENCES
Ringold et al.: Journal of Organic Chemistry (1956),
vol. 21, pp. 1333-1334.
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