DE1247309B - Process for the production of new pregnene compounds - Google Patents

Description

HJNDESREPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. Cl .:

C07C CO 7 J

German class: 1.2 ο -25/05

Number: 1 247 309

File number: A 45502IV b / 12 ο

Filing date: March 16, 1964

Opened on: August 17, 1967

The invention relates to the preparation of new steroid ketals of the following general formula

CH ₃

(Ri - C - Rs) "

In this formula, R, Ri and Ro denote hydrogen or lower alkyl groups, R3 denotes hydrogen, a lower alkyl group or a halogen atom, R4 denotes an alkanoyloxy group, R ₅ denotes a lower alkyl group and η denotes the number 0 or 1.

The new compounds of the formula given above are generally crystalline solid substances which Practically insoluble in water and in the usual organic solvents such as ether, benzene and Toluene, are somewhat soluble.

The new ketals of the general formula I given above are made by reacting a steroid compound the general formula

11

R ₅

in which R4 and Rj have the meanings given above own, with a glycol of the general formula

^ KJlX

(Ri-C-Ro) _n

R ₃ -C-OH H

III method of manufacturing new
Pregnen connections

Applicant:

American Cyanamid Company,

Wayne, N. J. (V. St. A.)

Representative:

Dr. I. M. Maas and Dr. W. G. Pfeiffer,

Patent Attorneys, Munich 23, Ungererstr. 25th

Named as inventor:

George Rodger Allen, Jr., Old Tappan, N. J .;

Martin Joseph Weiss, Oradell, N. J. (V. St. A.)

Claimed priority:

V. St. v. America May 17, 1963 (281 345)

in which R, Ri, R2, R3 and η have the meanings given above, preferably prepared at a temperature of 60 to 180 ^° C. in the presence of a strong acid and preferably an inert solvent.

The practical implementation of the process according to the invention starts from 3-keto steroids of the general formula II. For example, a 3,20-diketo-4-pregnen with an a, ß- or an a, y-glycol, such as ethylene glycol, 2,3-butanediol, 1,2-propanediol, chloroethane-1,2-diol, 2,2-diethyl-1,3-propanediol, 1,3-propanediol or 1,3-butanediol, in the presence of a strongly acidic catalyst, e.g. B. p-toluenesulfonic acid, implement. The reaction to prepare the new compounds is preferably carried out in an inert solvent, such as benzene or toluene, at reflux temperature for about 1 to 24 hours, preferably 4 to 8 hours. It is also advantageous here if the water formed as a by-product is removed from the reaction mixture as the reaction proceeds, so that the reaction proceeds as completely as possible. After the end of the reaction, the steroid ketal formed can be purified by filtration, extraction and crystallization and in some cases by chromatography. Such cleaning measures are carried out in a known manner.

709 637/711

The steroid ketals produced in accordance with the present invention do not show any remarkable ultraviolet absorption.

It has been found that the new compounds have a progestational effect and replace the known ones progestative steroid compounds such as progesterone for the treatment of, for example habitual abortion. The new compounds have the added advantage of being well effective when administered orally. When administering, for example, na-acetoxy-S-ethylenedioxy-6-methyl-5-pregnen-20-one Sexually immature female rabbits orally pretreated on estrogen once a day for 5 days surrenders after preparation the uteri for the histological examination (Clauberg examination) that the effect of a total dose from 0.1 mg of this substance to that of a total dose of 10 mg 17a-acetoxyprogesterone, a well known clinically used oral progestative agent. the Compounds obtainable according to the invention are also suitable as in connection with estrogenic agents oral contraceptives.

The following examples explain the process according to the invention.

25 Example 1

Production of na-acetoxy ^ -äthylendioxy-6-methyl-5-pregnen-20-one

A solution of 2.00 g of 17a-acetoxy-6a-methylprogesterone and 60 mg of p-toluene-sulfonic acid monohydrate in 100 ml of benzene and 16 ml of ethylene glycol is refluxed for 3 hours. The water that forms is removed using a Dean-Stark still. The cooled solution is poured into 100 ml of a 5% strength aqueous sodium bicarbonate solution. The organic phase is separated off, diluted with ether, washed with brine and water, dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure. The product obtained is recrystallized from acetone-petroleum ether (boiling range 60 to 70 ⁰ C) and recrystallized provides white crystals, mp = 185 to 187 ⁰ C; [a) l ⁵ - -55 ° C (c = 1.0, chloroform) with no noticeable ultraviolet absorption; λ ™ = 5.75, 5.85, 7.92, 7.98, 9.10, 8.30 µ.

When tested by the Clauberg method after oral administration to female rabbits found that the effect of this compound at a total dose of 0.1 mg of the activity of a total dose of 10 mg Ha-acetoxyprogesterone is equivalent.

Example 2

Production of 17a-acetoxy-3- (1,2-dimethylethylenedioxy) -5-pregnen-20-one

By reacting na-acetoxy-oa-methylprogesterone with 2,3-butanediol in the presence of p-toluenesulfonic acid according to the procedure described in Example 1, 17a-acetoxy-3- (1,2-dimethylethylenedioxy) -5-pregnen-20 is obtained -on from F. - 188 to 192 ⁰ C without noticeable ultraviolet absorption.

Claims (1)

Claim: Process for the preparation of new Pregnenverbindungen of the general formula CH ₃ (Ri - C - Ra) _n in which R, Ri and R2 are hydrogen or lower alkyl radicals, Rg is hydrogen, a lower alkyl radical or a halogen atom, R4 is an alkanoyloxy radical, R5 is a lower alkyl radical and η is the number 0 or 1, characterized in that one is in a manner known per se J ⁴ -3-ketone of the pregnane series of the general formula CH ₃ R ₅ with a glycol of the general formula R. H
- C - OH (Ri - C -R ₂ ), R, - C
H - OH preferably at a temperature of 60 to 180 ° C in the presence of a strong acid and preferably an inert solvent, where R, R] to R5 and η are as defined above.