Patent GB-1199605-A (GB)
Title: 13-Alkyl-18,19-Dinorpregn-4-en-3-one Compounds and their Derivatives
Inventor: TELLER DANIEL MYRON
IPC: C07J5/00
Filed: 1967-10-05
Abstract: 1,199,605. 13 - Alkyl - 18,19 - dinorpregnane compounds. AMERICAN HOME PRODUCTS CORP. 5 Oct., 1967 [4 April, 1967], No. 45471/67. Headings C2C and C2U. Novel steroids of the Formula (I) are prepared by hydrolysis of steroids of the Formula (II) (novel when X is CH.OH), prepared in turn by known methods. Preferred steroids (II) have the Formula (III), and these are prepared by reduction of steroids of the Formula (IV) (with subsequent 20-oxidation if required), prepared in turn by treatment of steroids of the Formula (V) with a base, with subsequent 20-reduction or -ketalization when required. (V) are in turn prepared by acylation of steroids of the Formula (VII) to give steroids of the Formula (VI) and oxidation of these. (I) can also be prepared by isomerization of steroids of the Formula (VIII) or oxidation of steroids of the Formula (IX) with isomerization of the product when required; with, when required, subsequent 20- reduction, 17-acylation or 17-hydrolysis. (VIII) are prepared by known methods, e.g. mild hydrolysis of (III). (I) can also be prepared from seco-steroids of the Formula (X) by an internal aldol condensation, followed, when required, by 20-reduction or 17-acylation; if cyclization is effected with, for example, pyrrolidine, the product is a 3-enamine, which can be hydrolysed to the 3-one. 3,20-Diones may be reduced to 3,20-diols and these oxidized to 20-ol- 3-ones. 20-Ols may be protected e.g. as tetrahydropyranyl ethers, before 17-ols are acylated. R is C 2-8  alkyl; R<SP>1</SP> is H or acyl; the steroids have the configuration of pregnanes or their enantiomers (including mixtures such as racemates); X is CO or a ketal thereof or CH(OH); Y is a hydrolysable protected oxo group accompanied by a #<SP>4-</SP>, #<SP>5-</SP> or #<SP>5(10)</SP>-double bond with or without a #<SP>2</SP>- or #<SP>3</SP>-double bond such as is convertible to a #<SP>4</SP>-3-one grouping by hydrolysis, with or without isomerization; Z is an optionally substituted aliphatic hydrocarbon group whose linkage to oxygen is stable to the action of an alkali metal in liquid ammonia; R<SP>2</SP> is acyl; X<SP>1</SP> is CO or CH(OH); and P and P<SP>1</SP> are oxo or protected, e.g. ketalized, oxo groups. The preparation of a starting material is as follows:-13#-ethyl-5-methoxy-des A-18,19-dinorpregna - 5,7,9 - trien - 20 - one # 3#- ethyl - 5 - methoxy - des A - 18,19 - dinorpregna- 5,7,9,17(20) - tetraen - 20 - ol acetate # 13# - ethyl - 17α,20# - epoxy - 5 - methoxy - des A - 18,19 - dinorpregna - 5,7,9 - trien - 20# - ol acetate # 13# - ethyl - 5 - methoxy - des A - 18,19 - dinorpregna - 5,7,9 - trien - 17α - ol - 20 - one # 13# - ethyl - 5 - methoxy - 20 - cycloethylene, or dioxy-des A-18,19-dinorpregna - 5,7,9 - trien - 17α - of # 13# - ethyl - 5 - methoxy - 20 - cycloethylenedioxy - des A - 18,19 - dinorpregna - 5(10),7 - dien - 17α - ol # 13# - ethyl - des A - 18,19 - dinorpregn - 9 - en - 17α - ol - 5,20 - dione # 13# - ethyl - 3N - pyrrolidinyl - des A - 18,19 - dinorpregna - 5(10),9(11)- dien - 17α - ol - 20 - one # 3 - chloro - 13# - ethyl - 18,19 - dinorpregn- 4,5 - seco - 2,9 - dien - 17α - ol - 5,20 - dione # 13# - ethyl - 18,19 - dinorpregna - 4,5 - seco - 9 - en - 17α - ol - 3,5,20 - trione # 13# - ethyl - 18,19 - dinorpregna - 4,5 - seco - 17α - ol - 3,5,20 - trione. All these compounds are racemates. The novel steroids (I) are progestational agents and androgen antagonists, and they may be made up into pharmaceutical compositions with suitable carriers.