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Патент USA US3098860

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3,098,850
Patented July 23, 1963
2
testosterone propionate while the androgenic activity was
about 25 percent that of testosterone propionate. The
novel compounds of this invention, because of their ana
bolic activity, are useful in increasing weight, muscle
strength, and for increasing the sense of well-being and
positive nitrogen balance in pituitary de?ciences. A
3,098,850
3-ENAM
DERIVATIVES 0F Zea-METHYL
Sa-ANDRGSTANES
John C. Babcock, Portage Township, Kalamatoo County,
' J Allan Campbell, Kalamazoo Township, Kalamazoo
County, and Raymond L. Pederson, ‘Kalamazoo, Mich,
assignors to The Upjohn Company, Kalamazoo, Mich,
favorable anabolic response can be achieved without
a corporation of Michigan
noticeable androgenic response owing to the high anabolic
androgenic ratio. They can be prepared and administered
10 in a wide variety of oral or parenteral ‘dosage forms sing
The present invention relates to novel steroid com
ly, or in admixture with other coacting compounds. They
pounds and is more particularly concerned with ‘20c
can be associated with a pharmaceutical carrier which
No Drawing. Filed Dec. 9, 1957, Ser. No. 701,347
3 Claims. (Cl. 260-4395)
methyl - 3 - oxygenated _ 17 - oxygenated-5u-androstane
can be a solid material or a liquid in which the compound
compounds, to novel intermediates in the production
thereof and to processes for the production of the novel
compounds and novel intermediates.
The novel compounds of the present invention can be
represented by the following formula:
tions can take the form of solutions, emulsions, sus
pensions, syrups or elixirs.
20
The process of the instant invention comprises treat
ing a 17-oxygenated-5a-androstan-3-one with a secondary
CH3
,
is dissolved, dispersed or suspended. The solid composi
tions can take, the form of tablets, powders, capsules, pills,
or the like, preferably in unit dosage forms for simple
administration or precise dosages. The liquid composi
R,
cyclic alkylene amine to produce the 3-enamine of the
corresponding starting material. The 3-enamine thus
produced is then allowed to react with a methylating agent
25 to produce the 2a-methyl-3-enamine compounds which
on hydrolytic removal of the enamine blocking group
yield the corresponding Za-methyl-d7-oxygenated-5a
(I)
androstan-3-one compounds.
wherein R is selected from the group consisting of
Reduction of these ,com
pounds with sodium borohydride produces the correspond
30 ing 3-hydroxy compounds which on acylation are produc
H
y
tive of the 3-esters thereof. During the acylation step,
a 17?-hydroxyl, when present, will also be acylated and
H
thereby be productive of the corresponding 3,17-diacylates.
wherein Ac is the acyl radical of an organic carboxylic
acid, preferably a hydrocarbon carboxylic acid contain 35 Similarly, acylation of the 2u-methyl-3-keto compounds
(before reduction with sodium borohydride) wherein a
ing from one to twelve carbon atoms, inclusive, and keto;
l7-hydroxyl is present, is productive of the corresponding
and wherein R’ is selected from the group consisting of
17-acylate.
\’
H’
\q
n’
0113'
wherein Ac is as above de?ned,
H0
,
Alternatively the compounds of the present invention
\
40
can be produced by reduction of the 4-double bond of
the corresponding 2iz-methyl - 17.- oxygenated-4-andro
sten~3-one U as more speci?cally illustrated by Examples
2 and 3. The saturated compounds thus produced can
then be reduced with sodium borohydriderto produce the
on,’
and keto.
It is an object of the invention to provide the novel
Zen-mBihYl - 3 - oxygenated - 17 - oxygenated-Sa-andro
45 corresponding 3_-hydroxy compounds. Acylation of the
hydroxy groups as described above is productive of the
corresponding 3- and l7-acylates and the 3,17-diacylates.
The compounds of the present invention can be pre
pared from l7l8-hydroxy 45a - androstan-3-one, 17,6-hy
stane compounds, particularly the 2a-methyl-5a-andro 50 droxy - 17a - methyl-5a-androstan-3-one, and Stat-andro
‘stane compounds represented by Formula I wherein R
stane-3,17,-dione, compounds well known in the art [see
is a ketone or a free or esteri?ed hydroxyl and wherein
Fieser and Fieser, Natural Products Related to Phenan
R’ is a ketone or a hydroxyl or a hydroxyl and methyl
threne, Reinhold Publishing Corp., New York (‘1949),
group, the hydroxyls being either free or esteri?ed. It
page 375].
is a further object of this invention to provide the novel 55
According to the process of the present invention, the
intermediates and methods for the production of the
ketone group at the 3-position of the above starting ma
novel compounds of this invention. Other objects of the
terial is converted to the corresponding 3-enamine deriva
present invention will be apparent to those skilled in
tive by reaction with a secondary cyclic alkylene amine.
the art to which this invention pertains.
The enamine formation can be carried out in accordance
The compounds of the present invention, compounds 60 with the disclosure of US. Patent 2,781,342.‘ Amines
represented by Formula I, are valuable therapeutic agents.
which can be used are cyclic amines such as pyrrolidine,
‘WT,
They exhibit anabolic-androgenic, progestational, and
gonadotropin inhibiting properties. They are especially
piperidine, C-alkyl substituted piperidines, e.g., 2,4-di
methylpyrrolidine, 3-isopropylpyrrolidine, 3,3-dirnethyl
useful as anabolic-androgenic agents and are of particular
pyrrolidine and the like. The preferred secondary amine
advantage in cases where selective anabolic activity is 65 is usually pyrrolidine. Although large molar equivalent
required because of their favorable anabolic-androgenic
excesses of the cyclic amine can be employed in the re
ratio. For example, 2u,17a-dimethyl - 175 - hydroxy-Sa
androstan-3-one was found to have an oral anabolic ac
tivity of over twice that of methyltestosterone and an
action, the preferred proportion of amine to starting
steroid is usually from about 1.1}to about seven moles of
amine per mole of steroid and especially from about 1.1
androgenic activity of less than methyltestosterone. Like 70 to two. Moisture in the reaction is detrimental to the
wise the anabolic activity of Zea-methyl-17?-l1ydroxy-5a
procurement of high yields of product, and preferred
androstan-B-oue was found to be about equal to that of
reaction conditions therefore include removal of the water
3,098,850
pounds is preferred. Any suitable temperature between
The reaction is preferably conducted above room tem—
about zero and 100 degrees centigrade may be employed,
with room temperature being satisfactory. Hydrogenation
perature, i.e., above about 25 degrees centigrade, e.g.,
between about 25 and 150 degrees centigrade. Reaction
is continued until approximately one molar equivalent of
hydrogen has been absorbed. The catalyst is then sep
arated from the solution by ?ltration and the hydrogenated
times can vary between about a'few minutes to several
days, depending in part upon the reaction solvent or
solvents, ratio of reactants, selected amine, water removal
and temperature. Reaction solvents employed are organic
solvents inert to the reaction such as benzene, toluene,
xylene, chlorobenzene, pentane, hexane, methylene chlo~
ride, carbon tetrachloride, methanol, ethanol, tertiary
butyl alcohol, tetrahydrofuran, dioxane, and the like.
4
or more is operative, a pressure of from about ten to 25
formed during the enamine formation by known methods.
products separated by conventional separation or extrac
tion procedures.
When reduction is accomplished with a metal such as,
10
The 3-enarnine of the corresponding starting material
thus produced is then methylated in a preferably dry
inert organic polar solvent such as ethanol, methanol,
isopropanol, butanol, dimethylformamide, and the like,
for example, lithium, sodium, potassium, and the like,
with lithium being prefered, the reaction is conducted in
, liquid ammonia for a period of a few minutes to about
four hours. A solvent such as, for example, ether, tetra
hydrofuran, methylene chloride and the like may be
employed if desired. On completion of the reaction, the
with an excess of methylating agent such as a methyl
ammonia is allowed to evaporate and the product is '
halide to produce the 2a-methyl-3~enamine of the corre
isolated ‘by conventional procedures such as ?ltration or
extraction with an organic solvent.
sponding starting material. Methyl halides thus employed
The thus-produced Za-methyl-l7-oxygenated-5a-andro
are those wherein the halogen is chlorine, bromine or 20
iodine with bromine and iodine generally preferred. A
preferred method is to treat the isolated and dried 3
enamine with an excess of methyl iodide in dry methanol
stan-3-one compounds are reduced at the 3-position with
a chemical carbonyl reducing agent in an organic solvent,
e.g., ethanol, methanol, isopropyl alcohol, and tetrahydro
furan, to produce the corresponding 3-hydroxy com
and re?ux until the reaction is complete. At the end of
the re?ux period, the excess methyl iodide is removed by 25 pounds, i.e., Za-methyl-Soc-androstane-3,17,8+diol, 2a,17cx
distillation. The S-enamine, preferably the 3-pyrrolidyl
enamine, of Zea-methyl-17f3-hydroxy-5a-androstran-3-one,
dimethyl-5a-androstane-3,l7B-diol, and 2a-methyl-3-hy
2u,17a-dimethyl-17B-hydroxy-5a-androstran - 3 - one, and
alkali metal borohydride or an alkali metal aluminum
droxy-5a-androstan-17-one. Reducing agents such as an
hydride, e.g., sodium borohydride, lithium aluminum hy-.
2a-methyl-5u-androstrane-3,17-dione thus produced can
then be hydrolyzed with water, aqueous acid or base, 30 dride, lithium borohydride, and the like, are operative.
The temperature of the reaction mixture is usually main
alkanols or alkanol water mixtures. This treatment re
tained between about zero and about 100 degrees centi
moves the 3-enamine group and results in regeneration of
grade with temperatures between about room temperature
the A4-3-keto group in the steroid nucleus, with produc
and the re?ux temperature of the reaction mixture being
tion of the Zea-methyl compounds of the corresponding
starting material. A preferred method for the hydrolysis 35 preferred for a period varying from a few minutes to
several hours. After the completion of the reaction, the
of the S-enamine group is in la methanol and ten percent
reaction mixture is preferably mixed with water or an
aqueous sodium hydroxide solution. The alkaline solu
tion is heated under re?ux for a few minutes and then
concentrated by distillation to remove most of the
acid to decompose any excess reducing agent and organo
metal complexes. The product is isolated by known meth
methanol present and cause precipitation of the product. 40 ods such as, for example, ?ltration or extraction with an
organic solvent.
If the product is not solid the hydrolysis mixture is diluted
with water and extracted with a water-immiscible solvent
The compounds of this invention, represented by For
such as methylene chloride, benzene, toluene, hexane, or
mula I, may be utilized either as the free alcohols or as
distillation giving the Zea-methyl compounds, i.e., Za-meth
at those positions, is accomplished by allowing the hy
the esters. Acylation of the hydroxyl groups either at the
the like. The combined solvent extractions are then
dried over a drying agent and the solvent removed by 45 3- or 17-positions when such hydroxyl groups are present
droxy compounds to react with the anhydride of an
organic carboxylic acid, preferably a hydrocarbon car
boxylic acid containing from one to twelve canbon atoms,
An alternate method for the preparation of the 20: 50 inclusive, for example, a saturated straight-chain aliphatic
yl-l7/8-hydroxy - 5a - androstan - 3 - one, 20:,170: - dimeth
yl-17?-hydroxy-5e-androstan-3tone, and Za-methyl-Sa
androstane-3,l7-dione.
methyl-17-oxygenated-5a-androstan-3-one compounds of
acid, e.g., acetic, propionic, butyric, valeric, hexanoic,
the present invention involves reduction of the 4-double
laun'c, a saturated branched~chain aliphatic acid, e.g.,
testosterone and 17a-methyltestosterone according to the
and p-toluic, a saturated dibasic acid (which can be con
trimethylacetic, isobutyric, isovaleric, a cycloaliphatic
bond of the appropriate Z-methylated starting materials
saturated acid, e.g., cyclohexane-carboxylic acid, an al
such as, for example, 2wrrnethyltestosterone, 2a,17a-di
methyltestosterone, and the like, which are prepared from 55 karyl acid, e.g., phenylacetic, Z-phenylpropionic, 0-, m-,
verted into water-soluble, e.g., sodium salts), e.g., succinic,
adipic, a monobasic unsaturated acid, e.g., acrylic, cro~
Chem., 21, 1333 (1956). The reduction can be accom
tonic, undecylenic, propiolic, cinnamic, a dibasic un
plished either by hydrogenation with hydrogen in the
presence of a catalyst such as palladium supported on 60 saturated acid (which can be converted into water-soluble,
e.g., sodium salts), e.g., maleic and citraconic. Illus
charcoal, barium sulfate, zinc oxide, calcium carbonate,
trative of the esters thus produced are the 3-monoacylatcs
and the like, or by a metal such as, for example, lithium
such as, for example, 2a-methyl-3-hydroxy-5a-androstan
in liquid ammonia.
17-one 3-acetate, 2u-methyl-3~hydroxy-i5aaandrostan-l7
The hydrogenation is usually conducted in a solvent
65 one 3-propionate, 2a-methyl-3-hydroxy-5a-androstan-17
medium. Alkanols, hexane, acetone, methyl ethyl ketone,
one 3-hemisuccinate, 2oz-methyl-3~hydroxy-5a-androstan
dioxane, acetic acid, ethyl acetate, or like organic solvents
17-one S-phenylacetate; the 17-monoacylates such as, for
may be advantageously employed, with tertiary butyl al
example, Za-methyl-l7,8-hydnoxy-ia-androstan-3-one l7
cohol being preferred. The catalyst can be reduced prior
acetate, 2cz-methyl-l7?-hydroxy-5a-androstan-3-one 17
to the introduction of the 2-methyl-A4-steroid or prefer 70 isovalerate, Za-methyI-l7l8-hydroxy-5a-androstan - 3 - one
ably the steroid, catalyst and supporting media can be
17 - propionate, Zea-methyl-17?-hydroxy-5a-androstan-3
contacted together in a solvent medium prior to introduc~
one 17-maleate; the 3,17-diacylates such as, for example,
procedures given by Ringold and Rosenkranz in J. Org.
tion of the hydrogen. It is not necessary to conduct the
reaction under pressure, although, when pressure is
utilized, a hydrogen pressure of about one to 100 pounds 75
2a,17a-dimethyl-5u-audrostane-3,l7/8-diol 3,17-diacetate,
2a,17u~dimethyl-5u-androstane-3,17B-diol 3,17-dipropio
nate, 2a,17u-dimethyl-5oc-androstane-3,l7?-tdiol 3,17-di—
3,098,850
6
crotonate, 2a,17a-dimethyl-5a-androstane-3,17,8-dio1 3,17
concentrated to dryness and the residue was chromato-i
dipropiolate, and the like.
graphed over 110 grams of synthetic magnesium silicate.
The following examples are illustrative of the process
and products of the present invention, but are not to be
The column was eluated with ninety milliliter fractions of
three percent acetone in Skellysolve B :hexanes. Fractions
construed as limiting.
'
26 to 36, inclusive, were combined and recrystallized from
acetone to give 129 milligrams of ZDL-II‘lBlIhYl-17?-l1YdI‘OXY
Example 1 .—2 a-Methyl-I 7?-Hydroxy-5a-Androstam
5‘oz-androstan-3-one identical to that obtained by the proce~
3-One
dure of Example 1.
A solution of four grams of 17?-hydroxy-5wandrostan
Example 3 .—2 0b,] 7a-Dimethy l-1 75-Hydr0xy-5 Ot
3-one in ?fty milliliters of benzene was concentrated by 10
Andr0stan-3-One
heating to 35 milliliters in order to remove any water
To 250 milliliters of liquid ammonia, which had been
present. Two milliliters of pyrrolidine was then added
dried with traces of lithium until a blue color remained,
and the solution was re?uxed, under nitrogen for one
was added 400 milligrams of lithium followed by a solu
and one~half hours, using a water trap to remove any
water formed in the reaction. After the re?ux period 15 tion of 2a,17a-dirnethyltestosterone in 48 milliliters of
anhydrous ether and four milliliters of tetrahydrofuran.
the reaction mixture was concentrated to dryness under
Addition of the 2a,17a-dimethyltestosterone solution was
reduced pressure to give 4.5 grams of the 3-pyrrolidy1
done dropwise over a period of thirty minutes. After
enamine of 17B-hydroxy-5a~androstan-3-one as a crude
stirring for an additional twenty minutes the mixture was
white solid having a melting point of 201 to 206 degrees
centigrade and a rotation of [oc]D plus 34 degrees (chloro 20 acidi?ed with the addition of ?ve grams of solid am
monium chloride and the ammonia was allowed to evapo~
rate oif. The residue was diluted with water and extracted
form).
A suspension of 3.9 grams of the enamine in twenty
‘milliliters of absolute methanol and ?ve milliliters of
with ether.
methyl iodide (dried ‘and vfreshly distilled) was re?uxed
dried, and evaponated to dryness to give 1.13 grams of
The ether extract was washed with water,
under nitrogen for three hours. The solid went into solu 25 solid 2a,17a-dimethyl-17?-hydroxy-5a-androstan - 3 - one
identical to that-obtained by the procedure of Example 1.
tion after ?fteen minutes of re?ux. The reaction mixture
An analytical sample melted at 134 to 136 degrees centi
containing the 3-pyrrolidyl enarnine of 2a-methyl-tl7l3
grade and had a rotation of [ab plus one (chloroform).
hydnOXy-Sa-andrOstan-S-Qne was then ‘concentrated to
Analysis.—Calculated for C21H34O2: C, 79.19; H. 10.76.
near dryness and was diluted with twenty milliliters of
Found: C, 7-8.63;H, 10.58.
ten percent sodium hydroxide solution and enough
methanol to make a total volume of sixty milliliters.
Example 4 .—2 a,] 7 a-DimeIhyI-S cc-A ndr0stane-3J 718-Di0l
(The resulting solution was heated under re?ux‘ for 25
A solution containing 1.66 grams of sodium borohy
-minutes and was then concentrated until a solid precipi
dride in seventeen milliliters of 0.1 N sodium hydroxide
tate formed. The solid was separated by ?ltration and
'was chromatographed over 100 grams of synthetic mag 35 was added to ‘a solution of 3.2 grams of 2oc,17a-dimethyl
17B-hydroxy-5a-androstan-3-one in 85 milliliters ,of
nesium silicate. The column was eluted with 250 milli
ethanol. After twenty minutes of stirring, the mixture
liter petroleum ether-acetone fractions as follows:
was diluted with 250 milliliters of water and Was acidi?ed
Fractions 1—3-—-two percent acetone in petroleum ether
to pH 6 by drop-wise addition of thirty percent acetic acid.
Fractions 4-15‘—three percent acetone in petroleum ether 40 The resulting solid precipitate Was collected by ?ltration,
Fractions 16-17——four percent acetone in petroleum ether
washed, and dried to give three grams of 212,17 a-dimethyl
Fractions 1'8-19--?ve percent acetone in petroleum ether
5a-androstrane-3,17-diol. Two recrystallizations from
acetone gave 0.70 gram of puri?ed product having a
Fractions 10 to 15, inclusive, were combined and evap
melting point of 176 to 178 degrees centigrade and a rota
orated to dryness to give 0.5 gram of 2a-methyl-17B
hydroxy-5a-androstan-3-one which on recrystallization 45 tion of [1x1]; minus 24 degrees (pyridine).
Analysis.——Calculated for C21H36O2: C, 78.69; H, 11.32.
Found: C, 78.48; H, 11.48.
Following the procedure above but substituting 2a
methyl-17/i-hydroxy-5a-androstan-3-one of Examples 1
from ether-Skellysolve B hexanes gave needle-like crystals
which melted at 151 to 153 degrees centigrade and had
a rotation of [a]D plus 29 degrees (chloroform).
Found:
AnalysiS.—Calculated
C, 78.93; H, 10.14.
for (320113202: C,
H,
50 and 2 as starting material therein is productive of 20a
methyl-5u-androstane-3,17B-diol.
Fractions 8 and 9 were combined and recrystallized
from ether-Skellysolve B hexanes to give dense prism-like
crystals which melted at 174 to 176 degrees centigrade.
Example 5 .—Za-Methyl-3-Hydroxy-S a-A ndrostan-l 7-One
Following the procedure of Example 4, reduction of
Infrared analysis showed this material to be a different
crystalline form of 2a~methyl-17/3-hydroxy-5oc-androstan 55 2a-methyl-5a-androstane-3,17-dione of Example 1 with
one equivalent of sodium borohydride gave a reduction
mixture which was chromatographed over synthetic mag
3-one.
Following the procedure above but substituting 5on
androstane-3,17,dione or 17,8-hydroxy-;17a-methyl-5oc-an
nesium silicate using Skellysolve B hexanes plus acetone
for elution of the column. The fraction which by in
drostan-3-one as starting material therein is productive
frared analysis showed the absence of a six membered
ring ketone was recrystallized from acetone to give a
of 2a-methyl-5a-androstane-3,17-dione and 2a,17a-di
methyl - 17,8 - hydroxy - 5a - androstan - 3 - one, respec
tively.
2a-methyl-3dhydroxy-5a-androstan-17-one.
The intermediate 3-pyrrolidyl enamine of 204
methyl-Sa-andrQStane-B,17-dione and 3-pyrrolidyl enamine
of 2a,17a~dimethyl-17B-hydroxy-5oc-androstan-3-one are
produced by the reaction.
Example 2.—2oc-Mez’hy l-1 7/3-Hydr0xy-5a-Androsz‘an
65
Example 6 .—2 0a,] 7a-Dimethyl-5a-Andr0stane-3,1 7B-Di0l
3,17-Diacetate
One gram of 2a,17a-dimethyl-5a-androstane-3,17/8-diol
grams of ?ve percent palladium on charcoal catalyst was
was dissolved in 22 milliliters of acetic anhydride and
the solution was heated under re?ux for one-half hour.
The excess acetic anhydride was then removed by distil
lation under reduced pressure and the resulting residue
was crystallized from methanol to give 2a,17a-dimethyl
hydrogenated with hydrogen at atmospheric pressure.
5a-androstane-3,17p-diol 3,17-diacetate.
3-One
A mixture containing 0.91 gram of Za-rnethyItestQs-ter
one, forty milliliters of t-butyl alcohol and ninety milli
Similarly, by allowing 2a,17a-dimethyl-5a-androstane
After 32 minutes when the theoretical amount of hy
drogen was taken up, the hydrogenation was stopped and
3,,l7?-diol to react with the appropriate hydrocarbon
the catalyst was removed by ?ltration. The ?ltrate was 75 carboxylic acid anhydride, for example, at temperatures
3,098,850
2a,17wdimethy1-5u-androstane-3,17/3-diol 3,17-dicinna
between 100 and 150 degrees centigrade, there are pro
duced other 3,17-diacylates such as, for example,
mate,
2oz,17uédirnethyl-5ot~androstane-3,175-diol 3,17-dimaleate,
2a,17a-dimethyl-5a-androstane-3,17/3-dio1 3,17-dipropio
nate,
and 2a,17a-dimethy1-5ot-androstane-Zi,17[3-diol 3,17-dicit
2a,17a-dimethyl-5u-androstane-3,17/3-dio1 3,17-dibutyrate,
2a,17ot-dimethyl-5a-androstane-S,17/3-di01 3,17-diva1erate,
raconate.
2a, 170L-dlII1ethYl-5 0t-8l1dI'OStE1I16-3, 17,8-dio1 3,17-dihexan0
diol, 2a-methy1-17,6-hydroxy-5u-androstan-S-one, 20:,1711
Similarly, acylation of 2a-methyl-5a-androstane-3,17
ate,
2a,17u-dimethy1-5a-androstane-3,17B-dio1 3,17-di1aurate,
2a,17a-dimethy1-5ot-androstane-3,17B-dio1 3,17-di-(tri
dirnethyl-17/3-hydroxy-5ot-androstan-3~one, and Zen-meth
10 yl-3-hydroxy-5a-androstan-17-one with the appropriate
hydrocarbon carboxylic acid anhydride is productive of
the corresponding 3,17-diacylates, 17-acylates, and 3-acyl
methylacetate) ,
2a,17a-dimethyl-5a-androstane-3,17,8-dio1 3,17-diisobutyr
ates, respectively. The preferred acylates are those cor
ate,
2a,17a-dimethyl-5oc-androstane-3,17?-diol 3,17-diisova1er
ate,
responding to the acylates described above for 2oc,17oc
15
It is to be understood that the invention is not to be
limited to the exact details of operation or exact com
2a,17a-dirnethyl-5a-androstane-3,17/3-di0l 3,17-dicyclo
hexane carboxylate,
2a,17a-dimethyl-5ot-androstane-3 ,17B-diol 3,17-dibenzo
ate,
2a,17ot-dimethyl-5a-androstane-3,17,8-diol 3,17-diphenyl
acetate,
20c, 17a-dimethy1-5 a-androstane-3, 17 ?-diol 3,17-di-(,B
phenyl ) -propionate,
pounds shown and described, as obvious modi?cations
and equivalents will be apparent to one skilled in the art,
20 and the invention is therefore to be limited only by the
scope of the appended claims.
We claim:
1. The 3-pyrro1idyl enamine of 2ot-methyl-175-hydroxy
I
2a,17u-dimethyl-5a-androstane-3,17,8-dio1 3,17-di-(o-, m-,
p-toluate),
2a,17a-dimethyl-Sa-androstane-3,17,B-diol, 3,17-diherni
5a-androstan-3-one.
25
3. The 3-pyrrolidy1 enarnine of Zu-methyI-Sa-andm
stane-3,17-dione.
2a,17a-dimethy1-5a-androstane—3,17B-dio1 3,17-dihemi
adipate,
.
30
References‘Cited in the ?le of this patent
Conf. on Metabolic Aspects of Convalescence, Trans.
ate,
2a,17a-dimethyl-Sa-androstane-E!,IZB-diol 3,17-diundec
ylenate,
2a,17u-dimethy1-5a-androstane-3,17p-dio1 3,17-dipropio
late,
2. The 3-pyrrolidyl enamine of 20¢,17oc-diII16tl1Yl-l7?
hydroxy-5a-androstan-3-one.
succinate,
2a,17a-dimethyl-5a-androstane-3,17(3-dio1 3,17-diacrylate,
2a,17u-dirnethy1-5a-androstane-B,17?-dio1 3,17-dicroton
dimet-hyl-S a-androstane-3, 17,8-dio1.
vol. 13, page 111 (1946), by Woodley et al., C.A., vol.
43, page 7124(g).
35
Fieser: Natural Products Related to Phenanthrene,
pages 423, 424, and 427 (1949).
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