Patent GB-1347145-A (GB)
Title: 17alpha-propadienyl steroids
IPC: C07J75/00
Filed: 1971-04-19
Abstract: 1347145 17α-Propadienyl-steroids SANDOZ Ltd 19 April 1971 [24 April 1970 21 May 1970 27 July 1970 4 Sept 1970 25 Jan 1971] 9930/71 Heading C2U [Also in Division A5] Steroids of the formula (wherein R 1  is C 1-3  alkyl, ring D is a 5- or 6- membered carbocyclic ring, and #p q represents the remainder of the steroid molecule with the proviso that this residue is other than that of the formula in which Z, embracing rings A and B and the substituents thereon, represents in which R 11  is H, C 1-3  alkyl, C 5-7  cycloalkyl, C 2-4  alkanoyl or tetrahydropyranyl, R 15  is H, 6α-CH 3  or 7α-CH 3  or, in the #<SP>6</SP>-compounds 6-CH 3 , R 16  is H or CH 3 , R 17  is H, F, Cl or CH 3  and R 18  is C 2-4  alkanoyl or is alkyl, when ring D is a 5-membered ring optionally 16α-hydroxy- or -C 2-4  alkanoyloxy-substituted, and with the further proviso that when ring D is a 5-membered ring unsubstituted at other than the 17- position then the residue #p q is other than a 3 - (C 1-4  - alkoxy) - 1,3,5(10) - trien - 11# - ol residue, a 3 - (C 3-7  cycloalkoxy) - 3,5(6) - diene residue or a 6-methyl-3-(C 3-7  cycloalkoxy)- 3,5(6)-diene residue) are prepared by reducing, with a hydride ion source, steroids of the formula wherein R 2  and R 3  are each C 1-3  alkyl or NR 2 R 3  is pyrrolidino, piperidino or homopiperidino, R 4  is C 1-4  alkyl and X<SP>(-)</SP> is the anion of a mineral acid (not HF), an alkyl sulphonic acid or an aromatic sulphonic acid. Novel products have the formula wherein R<SP>1</SP> 1  is CH 3 , C 2 H 5  or n-C 3 H 7 . These products may subsequently be oxidized to the corresponding 3-ones. The quaternary ammonium starting materials are prepared by quaternization of the corresponding tertiary amines containing a 17α-C# C.CH 2 .NH 2 R 3  side chain, which are in turn prepared (a) by reacting a corresponding 17α-ethynyl-17#-ol with an amine of the formula HO.CH 2 .NR 2 R 3  or with a mixture of formaldehyde and an amine of the formula HNR 2 R 3 ; or (b) by reacting a corresponding 17-keto steroid with an organo-metallic compound of the formula P.C#C.CH 2 .NR 2 R3, wherein P is an active metal or an active metal halide radical, e.g. -MgBr or -MgI, and hydrolysing the product. All the foregoing steroids may be normal or ring-altered steroids, e.g. A-homo, B-homo, C- homo, D-homo, A-nor, A-nor-B-homo, B-nor, C-nor and aza steroids such as 8-aza-steroids. Substituents in the rings are those that are standard in the steroid art, and they may be protected, when necessary, by known means. A mixture of 17α-ethynyl-estra-4,9-dien-3α,17#- and -3#,17#-diols is prepared bI NaBH 4  reduction of the corresponding 3-one. 3-Methoxy- 17α - ethynyl - estra - 1,3,5(10) - triene - 11#,17#- diol is prepared from 11#-hydroxy-estrone methyl ether and lithium acetylide-ethylene diamine complex. The steroids containing a 17#-hydroxy-17α- propadienyl grouping prepared by the method disclosed above, or other steroids possessing the said grouping which are prepared from them by hydrolysis to form a #<SP>4</SP>-3-keto grouping in ring A, variously possess estrogenic and progestational properties and may be made up into pharmaceutical compositions with suitable carriers. Specification 1,297,962 is referred to.