SU352889A1 - METHOD OF OBTAINING D-11-LZAESTRONA - Google Patents

Description

This invention relates to a method for producing a novel steroid compound d-11-azaestrone with valuable physiological properties.

In addition, d-11-azaestron can serve as an intermediate for the synthesis of d-11-aza analogs of other steroid hormones used in medicine, such as ethipylestradiol, dyrabolpna and noretinodrel.

Unlike the previously obtained methyl ester of 11-azaestrop and methyl esters of 9 (11) -hydro-11-azaestrogens, there are no additional modifications of the estrone molecule in the d11-azaestrone molecule, which reduce the hormonal activity of estrogens, and thus from d-11-azaestrone should expect higher activities.

There are known syntheses of other azasteroids, for example, 4-, 6-, and 8-azaestrogens.

Unlike these azaestrogens, which are racemic mixtures (rf /), according to the invention, d-11-azaestron is a natural tf-isomer, free of ballast yrimesi, usually a physiologically inactive / -isomer.

The method for the hydrolysis of methyl estrone estrone, which consists in treating pyridine prn hydrochloride with 210 ° C and used for the preparation of 6-azaestrone, was unsuitable for 11-azaanalogue, since

leads to a complex mixture of tarred products.

The proposed method for preparing d-11-azaestrone is that the d-l 1-estrone methyl ester is subjected to hydrolysis under acidic conditions, with the release of the target product with known n-nehm. For hydrolysis, the solution of hydrogen bromide in the acetic acid solution nrn 110 ° C is used. Under these conditions

d-11-azaestron is the only reaction product and the isolation of the target product of analytical purity is achieved by the addition of resinous impurities on a small amount of silica gel and crystallization,

without chromatographic procedures. The unambiguity of the chemical reaction and the ease of isolation and purification are especially important in the present case, because d-11-azaestron, which is resistant in the crystalline state, is unstable in hot solutions in organic solvents in the environment of oxygen, which makes it difficult to crystallize and chromatograph . The yield of d-11 azaestrone, but the proposed procedure, is 48.5%.

Example. A solution of 230 mg of d-11-azaestrone methyl ester (mp 189-90 C; ajg

9 hours at 110 ° C (ban). A mixture of tsmio regiapionpucho is evaporated to dryness in vacuo, the residue is dissolved in 20 ml of oxen and the addition of an aqueous ammonia solution to pM 8.5 is precipitated with 123 mg of isometric f / -l Lbaz-strone as a gray powder. Extraction of the solution with chloroform gave an additional 78 mg of the analogous product. In thin layers of .ro for mapping in ethyl acetate on a silnagel with 5% gypsum per wallpaper. Fractions of fractions were detected in pairs of gyut one nio with Rf 0.23 and slightly paired; in this system, the current methyl curve had an Rt of 0.34. The fractions are combined and dissolved. 5. "L ethyl acetate (|) is nlt after 100 mg of snlicker, doiolnit (;) washing: n () lightly | ethyletherm, and ((Mivirat is evaporated; repeat the filtering twice twice. Received 168 mg of yellow oil crystallizes when rubbed with 1i iodine with a small amount of ether and in 1 hour of washing the crystals on the filter with 1 ml of cold water

effmgr receive 106 mg (48.5%) of yellow crystals of f / -l i-azaestroia with t. Il. 191 - LUP), +130 (SO, 83, pyridi11), /} 219.5,265. 33-1 //./ (, 13; 3,80; 3.21); /. ;;. 221.5.2 (i2, 286, 327 w.u (IjvF 4.21, 3.74, d () 9, 3.34), v,

(OH, Nn); 1722 (C O); 1610;

3500, 3180 1585 and 1501

(arom, ring) s-1 /.

Found

about/

Wo: C, 75.35; 75.1 o; N 5.23; 5.12

Exact (dl

%: CiyHsiNO ,, H 7.80; N 5.16.

N oreme

The method of obtaining uf-11-azaestron, the difference between U (Liucfi and the fact that the hydroxy ester of rf-11-azaestroy is subjected to hydrolysis under acidic conditions with Byde. Heat of the desired product with known zrie. Small.