Patent GB-1416277-A (GB)
Title: 3-keto-7 a or beta-lower alkyl-delta5-steroids and process for preparing same
IPC: C07J7/00
Filed: 1973-02-22
Abstract: 1416277 7-Alkylsteroids RICHARDSONMERRELL Inc 22 Feb 1973 [20 March 1972] 8774/73 Heading C2U The invention comprises (A) compounds of formulae wherein R 1  is #-H, α-Me or #-Me with the proviso that when R 1  is α-Me the 9-H atom is #-oriented and that when R 1  is #-H or #-Me the 9-H atom is α-oriented; R 2 , R 2 <SP>1</SP> and R 3  are each H or Me; R 4  is C 1-3  alkyl; R 5  is H or oxo; R 6  is H, Me or Et with the proviso that when R 1  is α-Me then R 6  is H; R 7  is H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  alkadienyl, C 4-6  alkenynyl or C 4-6  alkadiynyl; R 8  is H, OH, C 1-12  acyloxy, 1-cyclopentenyloxy, 1-methoxycyclohexyloxy, or 2- tetrahydropyranyloxy, with the proviso that when R 7  is unsaturated then R 8  is other than acyloxy; or R, and R 8  together are oxo or ethylenedioxy; R 10  is H, Me or methylene; R 11  is H, Me, Et, OH, C 1-3  alkoxy, C 1-12  acyloxy or 2-tetrahydropyranyloxy, with the proviso that when R 10  is methylene then R 11  is other than acyloxy; or R 10  and R 11  together are di-(C 1-4  alkyl)methylenedioxy; R 12  is. H, OH, C 1-12  acyloxy, 1 - cyclopentenyloxy, 1 - methoxycyclohexyloxy or 2 - tetrahydropyranyloxy; R 13  is H; or R 12  and R 13  together are oxo; and n is 1 or 2 with the proviso that when R 6  is Me or Et then n is 1; (B) a process for preparing compounds of formula (wherein the symbols and provisos are as above, and substituents are optionally present at one or more of the 1,2,4,6,11,12,15,16,17 and, when present, 17a positions) from the corresponding 7-unsubstituted 4,6-dien-3-ones by reaction with a dialkylcopperlithium or a complex of an alkylcopper with a trialkylphosphine or trialkylphosphite in an inert anhydrous solvent at - 78 to + 10 C. After quenching the reaction mixture with a protonating agent (e.g. NH 4 Cl or oxalic or boric acid), the obtained mixture of 7α and 7# isomers may be separated by chromatography or fractional crystallization; and (C) the acid- or base-induced isomerization of compounds I and II to the corresponding #<SP>4</SP> compounds at room temp. to 100 C. Specified products are 7α-methyl-, 7#-isopropyl-, 7α,17α- dimethyl- and 7#,17α-dimethyl-testosterone. 17# - Hydrozyandrosta - 4,6 - dien - 3 - one, 17# - aceioxyandrosta - 4,6 - dien - 3 - one, androsta - 4,6 - diene - 3,17 - dione, 17α - methyl- 17# - hydroxyandrosta - 4,6 - dien - 3 - one, 17α - ethynyl - 17# - hydroxyandrosta - 4,6 - dien- 3 - one, androsta - 4,6 - diene - 3,11,17 - trione and pregna - 4,6 - diene - 3,20 - dione are prepared from the corresponding 4-monoenes 'by reaction with DDQ (Ex; 1,4,6,7,8,13,14). 17# - Propionyloxyandrosta - 4,6 - dien - 3 - one is prepared by esterifying the corresponding 17- ol (Ex. 5). 17,17 - Ethylenedioxyandrosta - 4,6 - dien - 3- one is prepared from 17,17-ethylenedioxyandrost-5-en-3#-ol by the successive actions of pyridinium hydrobromide perbromide, CrO 3 / py and LiCl/Li 2 CO 3  (Ex. 9). 17# - Hydroxyestra - 4,6 - dien - 3 - one is prepared from 3,17#-diacetoxyestra-3,5-diene by the successive actions of pyridinium hydrobromide perbromide, LiBr/Li 2 CO 3  and KOH/ MeOH (Ex. 11). 17# - Acetoxy - 6 - methylandrosta - 4,6 - dien- 3-one is prepared from 17#-acetoxy-6- methyleneandrost-4-en-3-one by refluxing with NaOAc/EtOH/Pd/C (Ex. 10). Compounds I and II are said to possess anabolic, androgenic, claudogenic, progestational, antiprogestational and antifertility properties, and may be made up with carriers into compositions for oral, parenteral, topical, rectal and vaginal administration.