Patent GB-1158332-A (GB)
Title: New 7alpha-Methyl-19-Nor-Androstadienes and process for their Manufacture
IPC: C07J1/00
Filed: 1966-07-25
Abstract: 1,158,332. 7α - Methyl 19 - nor - androstadienes. CIBA Ltd. 25 July, 1966 [30 July, 1965; 10 Sept., 1965; 27 June, 1966], No. 33284/66. Heading C2U. Novel steroids of the formula (wherein R is oxo or free, esterified or etherified #-OH with or without an α-aliphatic hydrocarbon group of up to 4 carbon atoms which may be substituted) are prepared from the corresponding #<SP>5'10'</SP>-steroids by bromination and dehydrobromination. In the products, a 17#-OH group may be esterified or etherified, or an esterified or etherified 17#-OH group hydrolysed; or a 17-oxo group may, after protection of the 3-oxo group, be converted to a 17α- hydrocarbyl-17#-OH grouping and the 3-keto group then liberated. The #<SP>5'10'</SP>-steroid starting materials may also be converted to the required products by microbiological 11 -hydroxylation, dehydration to the corresponding #<SP>5'01'</SP> <SP>9'11'</SP>-steroids and treatment of these with a mineral acid, or by conversion of the 11- hydroxy compounds to sulphonic acid esters thereof, and then treatment with an alkali metal salt of a lower aliphatic carboxylic acid. #<SP>4</SP> <SP>9</SP> - 7α methyl - 3 - oximino 17 - oxo - 19- nor-androstadiene is prepared by reacting 3,17- dioxo-7α-methyl-#<SP>4</SP> <SP>9</SP>-19-nor-androstadiene with HCN or a derivative thereof to convert the 17- oxo group to a cyanohydrin group, reacting the #<SP>4</SP> <SP>9</SP> - 7α   - methyl - 3 - oxo - 17 - cyano - 17#- hydroxy-19-nor-androstadiene with hydroxylamine or a lower alkyl hydroxylamine to give #<SP>4</SP> 9 - 7α - methyl - 3 - oximino - 17 - cyano - 17#- hydroxy-19-nor-androstadiene and then saponifying this. 3 - Oxo - 7a - methyl - 17# - hydroxy - #<SP>5'10'</SP>- 19-nor-androstene is prepared by hydrolysis of 3 - methoxy - 7α - methyl - 17# - hydroxy - #<SP>2</SP> <SP>5'10'</SP>- 19 - nor - androstadiene, prepared in turn by LiAlH 4  reduction of 7α-methyl-estrone methyl ether, to give 3-methoxy-7α-methyl- 17#-hydroxy- #<SP>1</SP> <SP>3</SP> <SP>5'10'</SP>-estratriene, and Birch reduction of this. 3 - Oxo - 7α,17α - dimethyl - 17# - hydroxy - #<SP>5'10'</SP>- 19-nor-androsfene is prepared by hydrolysis of 3 - methoxy - 7α,17α - dimethyl - 17# - hydroxy- #<SP>2</SP> <SP>5'10'</SP>-19-nor-androstadiene, itself prepared from the 17-ketone. The corresponding 17α-ethynyl compounds are prepared similarly. 3 - Methoxy - 7α - methyl - 11 - hydroxy - 17- ethylenedioxy - #<SP>2</SP> <SP>5'10'</SP> - 19 - nor - androstadiene is prepared by ketalizing 3-methoxy-7α-methyl- 17 - oxo - #<SP>1</SP> <SP>3</SP> <SP>5'10'</SP> <SP>9'11'</SP> - 19 - nor - androstatetraene (prepared by methylation of the 3-ol) to give the corresponding 17-ketal, reacting this with mchloro-perbenzoic acid to give 3-methoxy-7α- methyl - 9,11 - oxido - 17 - ethylenedioxy- #<SP>1</SP> <SP>3</SP> <SP>5'10'</SP>-19-nor-androstratiene, and reducing this with sodium in liquid ammonia; and is converted to the 17-ketone of the invention by dehydration with POCl 3  and hydrolysis with HCI. The 7α-methyl-steroids of the invention, which are stated to possess androgenic, anabolic, antigonadotrophic and gestagenic action, may be made up into pharmaceutical and veterinary compositions with suitable carriers.