close

Вход

Забыли?

вход по аккаунту

?

Патент USA US3063990

код для вставки
United States Patent 0
1
3,063,985
Patented Nov. 13, 19%2
2
formulas:
CH3
3,063,985
CYCLOPENTANOPHENANTHRENE COMPOUNDS
irssignments, to Syntex Corporation, a corporation of
Z/
anarna
10
i=0
“03'
John A. Zderic, Mexico City, Mexico, assignor, by mesne
N0 Drawing. Filed Dec. 15, 1960, Ser. No. 75,946
14 Claims. (Cl. 260-239)
on;
e0
5
AND PRGCESS
‘
---OR’
Rat/Y]
AMA]: ]
Z/ I
0:
()=
In the above formulas, R represents hydrogen, an alkyl
or an aralkyl group containing up to 12 carbon atoms,
The present invention relates to novel cyclopenta
nophenanthrene compounds and to a process for the 15 R’ represents hydrogen or a hydrocarbon carboxylic acyl
group.
production thereof.
Ac represents a hydrocarbon carboxylic acyl
group and Z indicates a double bond or a saturated link
More particularly, the present invention relates to
age between C—1 and (1-2.
The acyl groups ‘are derived from hydrocarbon car
l1a-aza-C-homo-l7a-hydroxy~A4-pregnene-3,20-dione, to
20 boxylic acids of less than twelve carbon atoms, saturated
lla-aza - C - homo - 17oz - hydroxy-A1’4-pregnadiene-3,20
dione, to acylated and N-alkylated derivatives thereof as
Well as to quaternary ammonium salts thereof.
The novel compounds of the present invention which
are hypotensive agents possessing progestational, anti
25
androgenic, anti-estrogenic, anti-ovulatory and anti
gonadotrophic activities are represented by the following
or unsaturated, of straight, branched, cyclic or cyclic
aliphatic chain, aromatic and may be substituted by
functional groups such as hydroxy, alkoxy containing up
to 5 carbon atoms, acyloxy containing up to 8 carbon
atoms, amino, nitro or halogen.
The novel compounds of the present invention may be
prepared by a process illustrated by the following equa
I19
m \m/
I
HO
I
HNAI
FQD
II
0 H3
é=o
Ac—N/\’ '
AcO- i
IV
III
0H3
MQJ,
3,083,985
3
'
Z'
4
on3
on,
I =0
--on
55:0
~03’
HN/\
-
v I
z
.
/\ii /
OHi\/
/
Ivrrr
O"
VII
20-dione or ester thereof With selenium dioxide in a
In the above formulas R’, Ac and Z have the same 15 solvent such as t-butanol and in the presence of catalytic
meaning as previously set forth.
_
amounts of pyridine to thus form lla-N-acetyl-C-horno
In practicing the process outlined above, the starting
A1A-pregnadien-17u-ol-3,ZG-dione or the esters thereof
compound 11,12-seco - 22a - A5-spirosten-3?-ol-11,12-dial
(I) is prepared by treating A5-22a-spirosten-35,12,8-diol
ll-one (disclosed by Rothman and Wall, J. Am. Chem.
Soc. 79, 3228 (1957) with lithium aluminum hydride
to form 11,63,125-dihydroxy diosgenin which upon reac
(VII: Z=double bond).
20
group is removed and there is formed lla-aza-C-homo-M
pregnen-l7a-ol-3,20-dione (VIII: Z=saturated linkage)
tion with lead tetraacetate in an inert solvent such as
benzene is converted into the 11,l2-seco-22a-A5-spirosten
3,6-ol-1l,12-dial (I). The dialdehyde is then reacted with
ammonia in ethanol solution thereby yielding a Schiff
base type intermediate which is then treated with lithium
Upon reaction of 11a-N-acetyl-M-pregnen-l7u-ol-3,20
dione with methanolic potassium hydroxide, the acetyl
25
which may be dehydrogenated at C—1,2 with selenium
dioxide to form 11a-aza-C-homo-NA-pregnadien-17a-o1
3,20-dione (VIII: Z=double bond). The latter com
pounds (VIII: Z=saturated linkage or Z=double bond)
may be acylated at C-l'lm as described above with con
aluminum hydride in tetrahydrofuran to form lla-aza-C- ,
current reacylation of the nitrogen moiety to form the
corresponding esters (VII).
spiroketal side chain is then e?ected by conventional
The novel lla-N-alkylated-C-homo compounds of the
procedure as by reaction with acetic anhydride at about
present
invention maybe prepared by a process illus
200°, oxidation of the resulting pseudo-compound to
trated by the following equation:
the diosone and alkaline hydrolysis and acetylation of
the latter thus forming 11a-N-acetyl-C-horno-A5'16-preg—
nadien-3l3-ol-20-one acetate (IV). The degradation of 35
CH3
CH3
homo-22a-A5-spirosten-3B-ol (II). Degradation of the
the side chain maybe preceded by acylation, preferably
I
acetylation, thus forming 3?-aeetoxy-1la-N-acetyl-C
homo-22a-A5-spirostene (III) which may then be sub
iected to degradation of the side chain to form the 11a
\1
°
Ac-N
N-acetyl-C-homo-A5rls-pregnadien - 3p - ol-20-one acylate
(IV).
/0
-
!
Bz_N
-
For introduction of the hydroxyl group at C-l'loz, the
16,17-double bond is ?rst epoxidized, preferably by reac
tion with aqueous alkaline peroxide in which case the
acyloxy group at C-3 is sapom'?ed, and there is formed 45
AcOQi
110 i
IV
X
lla-N-acetyl-C-homo - 16¢,17u - epoxy-A5-pregnen-3?-ol
ZO-one (V: R’zhydrogen). Reacylation with a hydro
- carbon carboxylic acid anhydride of less than 12 carbon
atoms, preferably acetic anhydride, affords lla-N-acetyl
CH3
C-homo - 16m,17m-epoXy-A5-pregnen-3B-ol-20-one acylate 50
‘is:
(V: R'=acyl). The latter compound may also be pre
Men
acylate
(IV) with t-butylhydroperoxide (see Yang, J. Am.
Chem. Soc. 80, 5845 (1958) whichrrreaction does not
an)
""" ‘'0
pared by epoxidizing the 16,17 double bond of Ila-N
acetyl~C-h0mo-A5,16-pregnadien - 318 - ol - 20 - one
CH3
55
affect the 3B-acyl group. The resulting 3j3-acyloxy-lla
N-acetyl-C-homo-16or,l7m-epoxy-A5-pregnen - 3B - o1 - 20
one (V: R'=acyl) is reacted with hydrogen bromide to
HO
i
‘—
an
110
i
XII
form the 16,8-bromo-17a-hydroxy grouping which upon
XI
treatment with Raney nickel results in reductive de
bromination and there is formed the 17a-hydroxy com
pound, 1 1a-N-acetyl-C—homo-A5-pregnene-3g3, 17a-di01-20
one acylate. Upon subsequent acid treatment, the acylate
group at C-3 is saponi?ed to form the free 35,175-(11'01.
By treatment with 8 N chromic acid, the 3?-hydroxy 65
treatment with acid the double bond at C-5,6 is shifted
atoms in benzenejsolution and in the presence of p-tolu
enesulfonic acid to form the 17a-acylate (VII: R'=acyl;
Z=saturated linkage).
A double bond can be intro
duced prior to or subsequent to the esteri?cation step by
re?uxing the 11a-N-acetyl-C-homo-A4-pregnei1-17a-ol-3,
CH3
i=0
"011
---~OH
an
group is' oxidized to the keto group and upon further
to 0-45, to form‘11a-N-acetyl-C-horno-A4-pregnen-17a
o1-3,20-dione (VI) which is then esteritied with a hydro
carbon carboxylic acid anhydride of'less than 12 carbon 70
CH3
HO
1
__-,
XIII
Moo
0: i
3,063,985
or
6
(IJH3
_
(‘1H3
0:0
0:0
1%
z , “ii
O:
To a mixture of 8.1 g. of 11,8,lZ?-dihydroxy-diosgenin,
140 ml. of glacial acetic acid and 210 ml. of thiophene
free benzene, 12.1 g. of lead tetraacetate were added
and the mixture was stirred at room temperature for
5 minutes. 200 ml. of Water containing 100 g. of sodium
acetate and 4 g. of sodium iodide were added, the color
was discharged by the addition of 80 ml». of saturated
aqueous sodium thiosulfate solution and the product
extracted twice, using each time 200 ml. of ethyl ace
tate. The pooled extracts were washed with aqueous
AM
I
z
O:
XVI
.
sodium bicarbonate and water, dried over anhydrous
sodium sulfate and evaporated to dryness. The residue
xv
was crystallized from a mixture of 60 ml. of methanol
and 12.5 ml. of water to afford l1,l-2-seco-22a-A5-spiro~
In the above formulas, Ac, R’, and Z have the same
meaning as previously set forth; R2 represents an alkyl 15 s-ten-3 18-01-1 1,12-dia1.
A mixture of 5 g. of the dialdehyde and 250 ml. of
or aralkyl group of up to 12 carbon atoms; R3 repre
ammonia-saturated ethanol was re?uxed during 10 hours.
sents a lower alkyl group and X represents a halogen
Upon evaporation of the solvent, a crystalline residue
such as iodine, chlorine or bromine.
was obtained which was re?uxed with 2.5 g. of lithium.
In practicing the process outlined above, lla-N-acyl
C - homo - A5,16 - pregnadien-3?-ol-20-one-3-acylate (IV), 20 aluminum hydride, in mixture with 250 ml. of'tetrahydro
furan during 20 hours. The excess of hydride was then
preferably 11a - N-acetyl-C-homo-A5,16-pregnadien-3B-ol
decomposed by careful addition of acetone, then a small
20-one-3-acylate, is reacted with ethyleneglycol in the
amount of saturated aqueous sodium sulfate solution
presence of p-toluenesulfonic acid to form the cyclic
and ?nally solid anhydrous sodium sulfate were added.
ethylene ketal derivitive. The latter compound is then
The solid was collected by ?ltration and the ?ltrate evap
re?uxed with lithium aluminum hydride in tetrahydro
orated to dryness under reduced pressure. Crystalliza
fu-ran to form the cyclic ethylene ketal of lla-N-ethyl
tion ‘from aqueous ethanol yielded l1a-aza-C-homo-22a
C-homo-A5,1G-pregnadien-3B-ol-20-one (X) which is then
A5—spirosten-3,8-ol.
hydrolyzed with acid to form lla-N-ethyl-C-homo-Aile
pregnadien-3B-ol-20-one (XI).
Example 11
A hydroxyl group is
then introduced at C-l7a in the same manner as set forth
4 g. of the latter compound was heated with 20 ml. of
acetic anhydride in a sealed tube at 200° C. for 55 min
utes; it was then cooled, the excess of anhydride was
hydrolyzed by the addition of 8 ml. of water and the
mixture was treated with 2 g. of chromium trioxide in
above for the N-acylated compound by epoxidizing with
aqueous alkaline peroxide, forming the 16p, 170t-bI‘OlI10
hydrin and reductively debr'ominating to ?nally obtain
lla-N-ethyl - C - homo - A5 - pregnen-B’?, l7a~diol-20~one
(XIII). The 3?-hydroxy group is oxidized to the S-keto
25 ml. of 80% acetic acid; after stirring for three hours
group with 8 N chromic acid and the MIG-bond is shift
ed to C-4,5 upon acid treatment thus producing lla-N
at room temperature, the mixture was diluted with water,
extracted with ether and the extract Was washed with
ethyl-C-homo-M-pregnen-l7a-ol-3,20-dione (XIV).
water, dried over anhydrous sodium sulfate and the ether
The tertiary hydroxyl group may then be ester?ed by 40 was evaporated. The residue was mixed with 200 ml. of
reaction with hydrocarbon carboxylic acid anhydrides in
60% acetone containing 2 g. of potassium hydroxide and
benzene solution and in the presence of p-toluenesulfonic
re?uxed for 5 hours, then concentrated to a small volume,
acid to form the 17a-acylates (XV: R’=acy1; Z=satu~
cooled,
diluted with water and extracted with ether. The
rated linkage).
extract ‘was washed several times with water, dried over
For introduction of a ‘double bond at C-l,2 the 11a
anhydrous sodium sulfate and evaporated to dryness.
N-ethyl-C-homo~A4-pregnen-l7a-ol-3,2O-dione or ester
Upon conventional acetylation, followed by recrystalliza
thereof is re?uxed with selenium dioxide as heretofore
tion from acetone-hexane, there was produced 3,8-acetoxy
described.
Quaternary ammonium salt derivatives of the forego
ing compounds XV are prepared by conventional reaction
1 1a-N-acetyl-C-homo—A5’16-pregnadien-20-one. '
Example III
2 g. of 11a-aza-C-homo-Z2a-A5-spirosteni3/3eol (de
with an alkyl or aralkyl halide in a solvent such as nitroal
kane to form compounds XVI.
There are obtained other N-acylated and N-alkylated
scribed in Example I) was treated with 2 ml. of acetic
anhydride in 10 ml. of pyridine at room temperature.
compounds by substituting for the N-acetyl group other
acyl radicals of the type mentioned previously.
The mixture was allowed to stand overnight and Was then
Thus
diluted with water, the solid was collected by ?ltration,
there are obtained N-acylated and N-alkylated com
pounds containing up to 12 carbon atoms such ‘as N
washed with water, dried and recrystallized from acetone
hexane thus aifording 3,6-acetoxy-1la-N-acetyLC-homo
propionyl, N-benzoyl, N-butyryl and the corresponding
N-propyl, N-benzyl and N-butyl derivatives.
22a-A5-spiroste'n. The latter compound was then treated
with acetic anhydride at 200°, the resulting pseudo~
The following examples serve to illustrate but are not
intended to limit the scope of the invention:
Example I
60
sapogenin oxidized to the diosone and was then treated
with potassium hydroxide and reesteri?ed as described
in Example II to thusyield 3?-aceto'xy-1la-N-acetyl-C
homo-A5,IG-pregnadienQO-One, identical with the com
A solution of 10 g. of A5-22a-spirosten-3B,12?-diol-1l
pound obtained in Example II.
one diacetate (Rothman and Wall, J. Am. Chem. Soc.
Example IV
79, 3228 (1957)) in 300 ml. of anhydrous tetrahydro 65
furan, was added dropwise to a suspension of 10 g. of
2 g. of 3,6-‘acetoxy-11a-N-acetyl-C-homo-AMfi-pregna
lithium aluminum hydride in 1 liter of anhydrous tetra
dien-20-one in 12 ml. of benzene, 1.0 ml. of Triton B
(benzyltrimethylammonium hydroxide, Midwest Labora
hydrofuran while stirring and the resulting mixture was
tories Inc.) and 1.2 ml. of t-butylhydroperoxide (Lucidol
re?uxed for 30 minutes. Acetone was added cautiously
to decompose the excess of hydride, then treated with 70 Division, Wallace and Tiernan, Inc.) were reacted at
room temperature overnight. The mixture was then di
aqueous sodium sulfate, ?nally with anhydrous sodium
luted with water, saturated with sodium chloride and
sulfate, the solid was ?ltered and the ?ltrate evaporated
extracted repeatedly with ether. The combined extracts
to dryness. The residue was triturated with hexane yield~
were dried over anhydrous sodium sulfate and evaporated
ing 1 1B,12B-dihydroxy-diosgenin.
75 to dryness. By crystallization from acetone~hexane, 3,8
3,063,985
acetoxy-l la-N-acetyl - 16a,17a-oxido-C-homo-A5-pregnen
20-one was obtained.
8
1 hour, ?ltered and the ?ltrate was evaporated. The
residue was puri?ed by chromatography on neutral alu
mina and the solid eluates were crystallized from acetone
.
Example V
hexane, thus giving 11a-N-acetyl-C-homo-A1»4-pregnadien
1.4 g. of the above compound in 16 ml. of glacial
l7ot-ol-3-20-dione.
acetic acid were treated with 3 ml. of acetic acid satu
rated with dry hydrogen bromide, stirring at room tem
perature for 1.5 hours. The mixture was then diluted
A solution of 500 mg. of the latter compound in 30
cc. of benzene was treated with 1 cc. of propionic anhy
dride and 1 g. of p-toluenesulfonic acid and the mixture
with ice water and the bromohydrin which precipitated
was kept at room temperature for 48 hours, the solution
was collected by ?ltration, washed with water and re 10 was then washed to neutral, dried over anhydrous sodium
?uxed with 10 g. of Raney nickel in 500 ml. of methanol
sulfate and evaporated to dryness. Recrystallization of
for 30 minutes. The nickel was removed by ?ltration,
the residue from acetone-ether gave lla-N-acetyl-C
the ?ltrate was evaporated to dryness and the residue
homo-A1A-pregnadien-l7a~ol-3,20~dione propionate.
crystallized from acetone-hexane thus furnishing 3?-ace
toxy- 1 1a-N-acetyl-C-homo-M-pregnen-17 a-ol-ZO-one.
Example IX
The 3-acetoxy group of the above compound was by
drolyzed by treating a solution of 1 g. of the compound
with 25 ml. of a 2.5% solution of perchloric acid in
methanol at room temperature during 18 hours. Subse
quent dilution with water and collection of the precipi
tate by ?ltration, ?nally water-washing, drying and re
15
A mixture of 2 g. of 3B-acetoxy-1l-a-N-acetyl-C-horno
A5116-pregnadien-20-one, 20 cc. of dry benzene, 16 cc.
of ethylene glycol and 300 mg. of p-toluenesulfonic acid
monohydrate was refluxed for 8 hours, using a Dean
Stark water separator. The cooled reaction solution was
washed with 5% aqueous sodium bicarbonate solution
and water to neutral, dried over anhydrous sodium sul
fate and the solvent was evaporated. Crystallization of
crystallization from acetone yielded free lla-N-acetyl-C
homo-A5-pregnene-3{3,l7a-diol-20-one.
the residue from acetone-ether afforded 20-ethylenedioxy
Example VI
To a solution of 2 g. of the above compound in 100 25
ml. of acetone, cooled in an ice bath was added a solution
of 8 N chrornic acid in dilute sulfuric acid in a slow
stream, with stirring and under nitrogen ‘until the color
of chromium trioxide persisted in the mixture. The
1 1 a-N-acetyl-C-homo-A5-16-pregnadien-3 ,B-ol-acetate.
A solution of 1 g. of the above 20-ketal in 30 cc. of an
hydrous tetrahydrofuran was added dropwise to a suspen
sion of 5 g. of lithium aluminum hydride in 300 cc. of
anhydrous tetrahydrofuran and the mixture re?uxed for
30 hours with stirring. Acetone was added cautiously to
product was precipitated by addition of water, collected 30 decompose the excess of hydride, then saturated aqueous
by ?ltration, water-washed, dried and crystallized from
sodium sulfate solution and ?nally solid anhydrous so
acetone-hexane to a?ord 1la-N-acetyl-C-homo-A5apreg
dium sulfate were added. The solid was ?ltered and
washed well with hot ethyl acetate, and the ?ltrate and
'1 'g. of the foregoing compound was treated in 10 'ml, 35 washings were evaporated to dryness under reduced pres
of acetone with a current of dry hydrogen chloride for
sure. Crystallization of the residue from acetone-hexane
1 hour at 20° C., the mixture was then poured into ice
gave ZO-ethylene ketal of 11a-N-ethyl-C-homo-Ail?-preg
water, the solid collected by ?ltration, washed with water,
nadien-3?-ol-20-one.
dried and crystallized from acetone-hexane. Thus 11a
A mixture of 600 mg. of the above compound in 20 cc.
nen-17a-ol-3,20-dione.
‘
'
'
N-acetyl-C-homo - A4 - pregnen-17 oc-O1-3 ,ZO-dione was ob
tained.
'
'
'
500 mg. of the above compound was allowed to react
for 1 hour at room temperature with '25 cc. of acetic
anhydride and 500 mg. of p-toluenesulfonic acid in 25 cc.
of acetic acid. The mixture was then poured into ice
water and the solid formed was collected, washed with
water, dried and crystallized from acetone-hexane, thus
producing 1 1a-N-acetyl-C-homo-AQ-pregnen-l7 :x-0l-3 ,20
dione
acetate.
~
7
a
a
7 Example VII
A solution of 0.4 g. of 3p-acetoxy-lla-N-acetyl-C
homo-A5116-pregnadien-2O-one in 16 cc. of methanol was
treated at 0° C. with 1 cc. of 35% hydrogen peroxide
and 0.4 g. of potassium hydroxide previously dissolved
in 1.6 cc. of water and the mixture kept at 0° C. for 70
hours, diluted with ice-salt water and extracted several
'times with ether. The combined extracts were washed
40 of 70% aqueous acetic acid was heated on the steam
bath for 30 minutes; the resulting solution was then
poured into dilute sodium hydroxide solution and the
formed precipitate collected by ?ltration, washed with
water and air dried.
There was thus obtained lla-N
ethyl-C-homo-A?’l6-pregnadien-3?-ol-ZO-one.
Example X
A solution of 2 g. of 1la-N-ethyl-C-homo-A5ym-pregna
dien-35-ol-20-one, 100 cc. of methanol was cooled to
15° C. and 5 cc. of 35% hydrogen peroxide was added.
A solution of 2 g. of sodium hydroxide in 8 cc. of water
was then added with stirring and cooling, at such a rate
that the internal temperature did not exceed 25° C.
After being allowed to stand at this temperature for 17
hours, the mixture was poured into ice-cold water, and
then acidi?ed with dilute hydrochloric acid. The formed
precipitate was collected, washed with water and dried,
with water to neutral, dried over anhydrous sodium sul
thus giving 1la-N-ethyl-l6u,17a-oxido-C-homo-A5-preg
fate and- evaporated to dryness.
nen-3?-ol-20-one.
The above compound was acetylated in a conventional
acetone - hexane
gave
Crystallization from
11a - N - acetyl-16a,17a-0xido-C
homo-A5-pregnen-3;8-ol-20-one.
,
i
_.
manner and the resulting 3-acetate was subjected to the
The above compound was treated with 2 cc. of pyridine
procedures of Examples V and VI, thus producing suc
and 2 cc. of acetic anhydride and the mixture was heated
on the steam bath for 1 hour; ,After the usual work-up,
cessively 11a-N-ethyl-C-homo-M-pregnene-3p,17a-diol-20
one 3—acetate, 1la-N-ethyl-C-homo-A5-pregnene-3B,17a
there was obtained 11a-N-acetyl-16a,17a-oxido-C-homo
A5-preguen-3?-ol-20-one acetate, identical with that ob
diol-20-one and 11a-N-ethyl-C-homo-M-pregnen-l7a-ol
3,20-dione.
tained in Example IV.
V
7 Example VIII
'
.
>
Treatment of the latter compound with selenium diox~
ide in t-butanol solution, in accordance with the method
of Example VIIl gave 11a-N-ethyl-C-homo-AlA-pregna
A stirred mixture of 1 g. of lla-N-acetyl-homo-M
pregnen-l7a-ol-3,20-dione, 50 cc. of t-butanol, 400 mg. 70 dien-17a-ol-3,20-dione.
Example XI
of selenium dioxide and- 0.3 cc. of pyridine was re?uxed
for 48 hours under an atmosphere of nitrogen, ?ltered
A solution of 1 g. of 11a-N-ethyl-C-homo-A‘s-pregnen
through celite, and the ?ltrate was evaporated to dryness
17a-ol-3,20-dione in 50 cc. of benzene was treated with
under reduced pressure. The residue was dissolved in
2 cc. of acetic anhydride and 1 g. of p-toluenesultonic
75
acetone, treated with decolorizing charcoal, re?uxed for
3,063,985
1t]
acid; the mixture was kept at room temperature for 48
hours, washed well with sodium carbonate solution and
water to neutral, dried over anhydrous sodium sulfate and
evaporated to dryness; by chromatography of the residue
bond between C-1 and 0-2 and a saturated linkage be
tween C-1 and C-2.
2. 11a-aza-C-homo-A‘i-pregnen-17a-ol-3,20-dione.
on neutral alumina and recrystallization of the solid 5
eluates from acetone-hexane, there was obtained lla-N
3. 1 1a-aza-C-homo-N'4-pregnadien- 17 a-ol-3,20-dione.
4. A compound of the following formula:
ethyl-C-homo-M-pregnen-l7a-ol-3,20-dione acetate.
CH3
Example XII
=0
A solution of 300 mg. of 11a-N-ethyl-C-homo-A‘i-preg
nen-17a-ol-3,20-dione acetate in 30 cc. of nitromethane
|___0 R,
Bro
was treated with 3 g. of methyl iodide and heated in a
sealed tube at 100° C. for 3 hours, concentrated almost
to dryness, diluted with a little cold ether and the precipi
tate was collected by ?ltration, thus giving the metho 15
iodide of 11a-N-ethyl-C-homo-A4-pregnen-17a-ol-3,20
dione acetate.
In a similar manner, 11a-N-ethyl-C-homo-AM-pregna
dien-17a-ol-3,20-dione was converted into the metho
wherein R’ is selected from the group consisting of hydro
iodide of l1a-N-ethyl-C-homo-Al'4-pregnadien-17a-ol-3,
gen and a hydrocarbon carboxylic acyl group of less than
ZO-dione.
12 carbon atoms; Z is selected from the group consisting
2/
Example XIII
1 g. of lla-N-acetyl-C-homo-A4-pregnen-17ot-ol-3,2O—
of a double bond between C-1 and C-2 and a saturated
linkage between C—1 and C-2; and R2 is selected from
the group consisting of alkyl and aralkyl containing up to
dione, obtained as described in Example VI was re?uxed
for 48 hours under an atmosphere of nitrogen with 50
cc. of 4% methanolic potassium hydroxide solution and
then neutralized with acetic acid. Part of the solvent
12 carbon atoms.
5. 11a-N-ethyl-C-homo-A4-pregnen-17a-ol-3,20-dione.
6. 11a — N - ethyl-C-homo-Al-4-pregnadien-17a-ol-3,20
dione acetate.
was removed under reduced pressure, water added and
7. The lower alkyl quaternary ammonium salts of a
then extracted with methylene chloride, the organic ex
compound of the following formula:
tract washed to neutral, dried over anhydrous sodium sul 30
fate and evaporated to dryness. Chromatography of the
residue gave the pure l1a-aza-C-homo-M-pregnen-l7a-ol
CH3
3,20-dione.
By the same method, but using lla-N-acetyl-C-homo
All‘i-pregnadien-17a-ol-3,ZO-dione (cf. Example VIII) as 35
5:0
LN/\ | “OR,
starting material, there was obtained lla-aza-c-homo-Aly‘l
., I I3
pregnadien-l7a-ol-3,20-dione.
Example XIV
By following the esteri?cation method of Example XI,
40
0:
the compounds obtained in the preceding example were
converted into the corresponding 11,17-diesters, namely
11a - N - acetyl - 17a. - acetoxy-C-homo-A‘Lpregnene-3,20
wherein R’ is selected from the group consisting of hydro
gen and a hydrocarbon carboxylic acyl group of less than
12 carbon atoms; R2 is selected from the group consisting
Example XV
of alkyl and aralkyl containing up to 12 carbon atoms;
and Z is selected from the group consisting of a double
By following the method of Example XI, but using
bond between 0-1 and C-2 and a saturated linkage be
cyclopentylpropionic anhydride instead of acetic anhy
dride 1la-\l-ethyl-C-hon1o-A‘Lpregnen-17ot-ol-3,20-dione, 50 tween C-1 and C-2.
dione and 11a-N-acetyl-l7a-acetoxy-C-homo-Al,4-pregna
diene-3,20-dione.
8. The methoiodide of 11a-N-ethyl-C-homo-M-pregnen- -
11a - N - acetyl-C-homo-All4-pregnadien-1711-01-3,ZO-dione
l7oc~Ol-3,20-dl0116 acetate.
9. The methoiodide of 11a-N-ethyl-C-homo-A1'4-preg
were converted into the corresponding cyclopentylpro
pionates.
nadien-l7a-ol-3,20-dione.
Example XVI
By following the method of Example XI, but using pro
10. A compound of the following formula:
pionic anhydride as esterifying agent, 500 mg. of Ila-aza
C-homo-A‘Lpregnen-17a-ol-3,20-dione were converted into
CH3
lla-N-propionyl - 17a - propionoxy-C-homo-A4-pregnen
3,20-dione.
I claim:
1. A compound of the following formula:
ta
2/
65
0:
Z Hrd
U
wherein R’ is selected from the group consisting of hydro
gen and a hydrocarbon carboxylic acyl group of less than
12 carbon atoms; Z is selected from the group consisting
of a double bond between C—1 and C-2 and a saturated
linkage between (3-1 and C-2; and Ac represents a hydro~
carbon carboxylic acyl group of less than 12 carbon
wherein Z is selected from the group consisting of a double 75 atoms.
3,063,985
11‘
12
7 l1. 11a-N-acetyl-C-homo-A4Lpregnen-17u-ol-3,2O-dione
14. A compound of the following formula:
acetate.
'
12. 11a 1 N - acetyl L C - homo - A13 - pregnadien - l7a-
ol-3,20-dione propionate'.
'
13. A compound of the following formula:
‘
" 1
'
'
CH
'j ’ (g 3
5 r
=0
15 wherein R2 is selected from the group consisting of alkyl
R'O
and aralkyl containing up to 12 carbon atoms.
1w
wherein R’ is selected from the group consisting of hydrogen and a hydrocarbon carboxylio acyl group of less than
12 carbon atoms; and Ac represents a hydrocarbon car- 20
boxylic acyl group of less than 12 carbon atoms.
"
'
x
-
Resume“ Clted m the the of this patent
UNITED STATES PATENTS
2,806,028
2,806’029
Mazm. _______________ __ Sept. 10, 1957
Mamr ______________ __ Sept. 10, 1957
Документ
Категория
Без категории
Просмотров
0
Размер файла
677 Кб
Теги
1/--страниц
Пожаловаться на содержимое документа