Patent GB-1292171-A (GB)
Title: 6-substituted-16-alkyldene-steroids of the pregnane series
IPC: C07J7/00
Filed: 1970-06-08
Abstract: 1292171 6 - Alkoxy - 16 - alkylidene steroids SCHERICO Ltd 8 June 1970 [9 June 1969] 27644/70 Heading C2U Novel steroids of the formula wherein R is C 1-6  alkyl; R<SP>1</SP> is H or C 1-6  alkyl; X is H, F or Cl; Y is G 1-8  acyloxy; and Z is -CH 2 -CH 2 - or are prepared (a) by reacting the corresponding 6-unsubstituted 6,7-saturated steroids or 3- enol ethers or esters thereof with more than 2 molecular equivalents of a cupric halide in the presence of an alkanol ROH; or (b) by reacting the corresponding 6-keto steroids preferably prepared by hydrolysis of the 6-methoxy products prepared for example by process (a) with a lower alkanol ROH or an appropriate lower alkyl ortho ester; or (c) for 1α,2α-methylene products, by reacting the corresponding #<SP>1,4</SP>'<SP>6</SP>- steroids with a methylene transfer agent such as dimethyl sulphoxonium methylide; or (d) by acylation of the corresponding 17α-ols; or (e) for 21-halo products, by halogen exchange of corresponding 21-iodo or -bromo steroids with a metal fluoride or chloride in an organic solvent; or (f) for 21-unsubstituted products, by reduction of the corresponding 21-iodo steroids. 6 - Methoxy - 16 - (methylene, ethylidene and n - butylidene) - 17α - hydroxy - 4,6 - pregnadiene- 3,20-diones are prepared from 16-alkylidene- 17α - hydroxy - 4 - pregnene - 3,20 - diones by method (a) above. On dehydrogenation with DDQ the 16-methylene compound gives 6- methoxy - 16 - methylene - 17α - hydroxy - 1,4,6- pregnatriene - 3,20 - dione, which is also obtainable by hydrolysis of 6 -methoxy- 16-methylene- 17α - acetoxy - 1,4,6 - pregnatriene - 3,20 - dione, itself prepared by dehydrogenation of 6- methoxy - 16 - methylene - 17α - acetoxy - 4,6- pregnadiene - 3,20 - dione or by acetylation of 6 - methoxy - 16 - methylene - 17α - hydroxy- 1,4,6 - pregnatriene - 3,20 - dione. Another compound prepared by dehydrogenation is 6 - methoxy - 16 - methylene - 17α - caproyloxy- 1,4,6 - pregnatriene - 3,20- dione and others prepared by acylation are 6 - methoxy - 16- methylene - 17α - (valeryloxy and butyryloxy)- 1,4,6 - pregnatriene - 3,20 - diones. 16 - (nbutylidene and ethylidene) - 17α - acetoxy - 4- pregnene - 3,20 - diones are prepared from 5,16 - pregnadien - 3# - ol - 20 - one 3 - acetate via 16α - (n - butyl and ethyl) - 5 - pregnen- 3# - ol - 20 - one 3 - acetates, the corresponding 17α - bromo compounds, 16 - (n - butyl and ethyl) - 5,16 - pregnadien - 3# - ol - 20 - one 3-acetates, the corresponding 16α,17α-oxido compounds, 16# - (n - butyl and ethyl) - 16α,17α- oxido - 4 - pregnene - 3,20 - diones and 16- (n - butylidene and ethylidene) - 17α - hydroxy- 4 - pregnene - 3,20 - diones. The corresponding caproates and propionates are prepared similarly. 16 - Methylene - 17α - alkanoyloxy - 21- chloro - 4 - pregnene - 3,20 - diones are prepared by reacting 16# - methyl - 16α,17α - oxido - 21- chloro - 4 - pregnene - 3,20 - dione (prepared from the corresponding 21-iodo steroid) with alkanoic acids in the presence of trifluoroacetic anhydride; or by acylation of 16-methylene- 17α - hydroxy - 21 - chloro - 4 - pregnene - 3,20- dione, itself prepared from the corresponding 21 - iodo compound. 3 - Ethoxy - 16 - (methylene, ethylidene and n-butylidene)-17α-acetoxy- 3,5-pregnadien-20-ones are prepared by enol etherification. 3,17α - Diacetoxy - 16 - methylene- 3,5 - pregnadien - 20 - one is prepared from 16# - methyl - 16α,17α - oxido - 4 - pregnene- 3,20 - dione. 1α,2α - Cyclomethylene - 6 - methoxy - 16 - (methylene, ethylidene and n - butylidene) - 17α - hydroxy - 4,6 - pregnadiene - 3,20 diones are prepared from the correspondi g 1,4,6- pregnatrienes. 6 - Methoxy - 16 - methylene - 17α- hydroxy - 21 - ( fluoro and chloro) - 4,6 - pregnadiene - 3,20 - diones are prepared by method (a) above. 16 - Ethylidene - 17α - acetoxy - 21- (chloro and fluoro) - 4 - pregnene - 3,20 - diones are prepared from 16#-ethyl-16α,17α-oxido-21- iodo - 4 - pregnene - 3,20 - dione (from the 21- unsubstituted compound) via 16# - ethyl - 21- (chloro and fluoro) - 16α,17α - oxido - 4 - pregnene - 3,20 - diones. 6 - Alkoxy - 16 - alkylidene- 17α - acetoxy - 21 - (fluoro and chloro) - 1,4,6- pregnatriene-3,20-diones are prepared by #<SP>1</SP> dehydrogenation. The steroids of the invention, which are stated to possess progestational and anti-androgenic properties, may be made up into pharmaceutical compositions with suitable carriers.