SU394366A1 - METHOD OF OBTAINING Av1,21-20-KETO-21-HOMOSTEROIDS - Google Patents

Description

The invention relates to a method for the preparation of new compounds - A821-20-keto-21-homosteroids, referred to as i-hc to the class of physiologically active A-1-20-keto-21-homosteroids.

There are ways to get the A21-20 obtaining the desired product) or 21-methyl dialkylamino as chlorine 1drate is heated with alkyl bromide and potassium acetate (or the resulting product is obtained).

The difference between the proposed method and the known method consists in treating Aie-21-methylaminodialkyl derivative with a mixture of acetic anhydride and acetic acid instead of revolving it into a quaternary axis in the known synthetic form. This difference in processing turned out to be quite significant, since the ion conversion of the Aie-21-methylaminodialk derivative to the quaternary axis was unsuccessful.

Mosteroids possessing a potential biologic activity are the essence of Yup1, nxc, which are the starting points for the synthesis of high-activity mineralocortic fungi. The presence in L - 1-20-keto-21-homosterdes of highly reactively coexistent ketodiene group and allows the preparation of steroid compounds on their base, iiecynj, He additional oxygen, nitrogen, sulfur containing substituents

physiologically active compounds with a wide cneixTpoM de | 1ST11i.

A method for producing A1 --- 20-keto21-th. A steroidoid is proposed, consisting in that A1-dehydro-20-keto-21-homoosteroid is iodon

in liarpeBaiHui, with chloricndrate dialkylamine and formaldehyde, the resulting 21-methyl dialkylamino derivative is boiled with a mixture of acetic anhydride and acetic acid to form a mixture of n products

treated with anhydrous potassium acetate in dimethylformamide and 100-110 ° C, and the desired product isolated by the use of n.

Mandehu suitable for

16-degpdro-20-ketosteroid and conduct with chlorhydrate to one alkyl n formaldehyde

: The application of the Maniheh reaction to 16-dehydro20-ketones has not been previously described. ; By way of example, the following are obtained: Acryl Acid 3-acetate 2151-21-homopregatrienol-3 | 3-lea-20 from dehydroirigeneepolon acetate.

3-Acetate 21-methyldimethylamino-D5 i (; - nperadienol-3 | 3-one-20.

A mixture consisting of 3 g of dehydroPregnenolone 3-acetate, 3.3 g of dimestylafsh hydrochloric acid, 65 ml of acetic acid and 3.3 ml of for4alin is heated at 95 ° C for 3 hours and kept at 20 ° C for 18 hours. ; The solvent is then evaporated in vacuo, ethyl acetate is added to the residue and it is extracted with 0, HCl solution. The aqueous layer is treated with a saturated solution of NaHCOs (to pH 8-9) and extracted multiple times with ether and CHCl3, the extracts are evaporated in vacuo. The residue (2.78 g) was dissolved in a mixture of hexapes: ether - 2: 1 and passed through a column of HOC3 under nitrogen pressure and evaporated. Crystallization of the residue from hexane yielded 2.43 g of 3-adatate 21-methyldimethylamino - A Yu-prediadiene - Sp-one-20 (yield 70%), so pl. 80 ° C;

IR (v), cm-1: 1730, 1665, 1590, 1390, 1370, 1245 in KBr;

UV spectrum: Uax 244 nm (V-11880); , 8 ° (in СНС1з, с 1,2).

Found,%: C 75.49; H 9.39; N 3.51

.

Calculated,%: C 75.54; H 9.44; N 3.39.

3-Acetate - Dz.1e.2i21 - homopregatrienol-Zran-20.

A solution of 1.5 g of 3-acetate, 21-dimetplaminomethyl-A- .10-pregladiol-3,6-one-20 in 7.5 ml of glacial acetic acid and 7.5 ml of acetic anhydride is heated at the boil for 2 hours. After cooling, the reaction mixture was diluted with IL and extracted with ether. The extract is evaporated in vacuo. 1.1 g of an oily residue are obtained, which is dissolved in a mixture of ethnr: hexa-1: 1 and is passed through a column with evaporated under nitrogen pressure. The residue (1.05 g) is dissolved in 25 ml of DMF, 1 g of freshly melted CH-COOK is added and the irn is heated at 105-110 ° C for 7.5 hours. After cooling, the reaction mixture was diluted with water and extracted with ether. Extracts evaporated B vacuum. The residue (850 mg) was dissolved in ether: hexane-1: 1.5 and passed several times through an AIoO column under nitrogen pressure. After evaporation of the solvents (1 lucha) from 0,70 g of 3-acetate-A 1 to 21-21-homopreg 1-acrpol-3p-opa-20 (yield 51%) with mp. 135-137 ° C (from hekean);

PC spectrum (v), cm-1: 1735, 1660, 1610, 1585, 1255 in KBr;

UV spectrum:) „groin 260 nm (e 11300); ., „А.х 33 nm (); -22 ° (in CnCi: i, s, - 0.9).

Paydeno,%: C 78.14; II 8.88. SmPz.O;,.

Calcined,%: C 78.26; H 8.69.

Subject invention

1. A method of producing A1 ' -g1-20-keto-2 -homoteroids, characterized in that the Av-dehydro-20-ketotsroid is reacted with chlorine phosphate dialkyl and formaldehyde, the resulting 21-methyl dialkylamino product is boiled with a mixture of acetic acid and formaldehyde, and the resulting 21-methyl dialkylamino product is boiled with a mixture of acetic acid and formaldehyde, and the resulting 21-methyl dialkylamino product is boiled with a mixture of acetic acid and formaldehyde, and the resulting 21-methyl dialkylamino product is boiled with a mixture of acetic acid and formaldehyde, and the resulting 21-methyl dialkylamino product is boiled with a mixture of acetic acid and formaldehyde, and the resulting 21-methyl dialkylamino product is boiled with a mixture of acetic acid and formaldehyde, and the resulting 21-methyl dialkylamino product is boiled with a mixture of acetic acid and formaldehyde, and the resulting 21-methyl dialkylamino product is boiled with a mixture of acetic acid and formaldehyde; the product mixture is treated with anhydrous potassium acetate in dimethylformamide and the desired product is isolated with known.