Patent GB-1228801-A (GB)
IPC: C07C/
Filed: 1968-06-25
Abstract: 1,228,801. 13 - Ethyl - 9#,10α - steroids. PHILIPS GLOEILAMPENFABRIEKEN N.V. 25 June, 1968, No. 30148/68. Heading C2U. The invention comprises compounds of Formulµ I and V wherein R 1  and the associated broken lines in rings A and B represent a 3-oxo, 3-oxo-#<SP>4</SP>, 3-oxo- #<SP>1#4</SP>, 3-oxo-#<SP>4#6</SP>, 3-oxo-#<SP>1#4#6</SP>, 3-H 2 -#<SP>2#4#6</SP>, 3-OR- #<SP>4</SP>, 3-OH-#<SP>4#6</SP>, 3-OR<SP>1</SP>-#<SP>3#5</SP> or 3-OR<SP>1</SP>-#<SP>2#4#6</SP> system where OR represents a hydroxy, C 1-6  alkoxy, C 3-6  cycloalkyloxy, aralkoxy or C 1-20  acyloxy group and OR<SP>1</SP> represents a C 1-6  alkoxy, C 3-6  cycloalkyloxy, aralkoxy or C 1-20  acyloxy group; R 2  is H, halo, C 1-6  alkyl or spirocyclopropyl; R 3  is H; or R 2  and R 3  together represent a 6,7-methylene group; R 4  is H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, fluoroethynyl, chloroethynyl or bromoethynyl; R 5  is a hydroxy, C 1-6  alkoxy, C 3-6  cycloalkyloxy, aralkoxy or C 1-20  acyloxy group; and R<SP>2</SP> 1  and the associated broken lines in rings A and B represent a 3-oxo- #<SP>4</SP> or 3-oxo-#<SP>4#6</SP> system. Compounds of Formula I are prepared (i) from corresponding 17-oxo compounds by reduction or by introduction of a 17α -substituted-17#-OH grouping, or (ii) by hydrogenating 6-methylene or 6-dihalomethylene compounds to 6-methyl compounds or (iii) by converting 6-methylene compounds to 6-spirocyclopropyl compounds. Compounds of Formula I are interconverted by (i) esterification or etherification of 17#-OH, (ii) 1,2-dehydrogenation, (iii) 6,7-dehydrogenation, (iv) enol esterification or etherification of 3-oxo, (v) 6-halogenation, (vi) 6,7-methylenation, (vii) hydrogenation of 17α-alkenyl or alkynyl, (viii) conversion of 3-OR-#<SP>4#6</SP> to 3-H 2 -#<SP>2#4#6</SP>, (ix) reduction of 3-oxo to 3-hydroxy and (x) oxidation of 3-hydroxy to 3-oxo. Compounds of Formula V are prepared by oxidizing corresponding 17-ethylidene compounds. A #<SP>4</SP>-compound of Formula V may be oxidized to the corresponding #<SP>4#6</SP>-compound. 18 - Methyl - 9#,10α - pregna - 4,17(20) - dien- 3-one is prepared from 18-methyl-9#,10α progesterone via 18 - methyl - 9#,10α - pregn - 4 - en- 3#,20α,-diol and 18-methyl-20α-hydroxy-9#,10α- pregn-4-en-3-one. The 17α-methyl, 17α-allyl and 17α-methallyl derivatives of 3-pyrrolidino-18-methyl-9#,10α- androsta-3,5-dien-17#-ol are prepared from 18- methyl - 9#,10α - androst - 4 - ene - 3,17 - dione via 3 - pyrrolidino - 18 - methyl - 9#,10α - androsta-3,5-dien-17-one. 6 - Methylene - 17# - acetoxy - 18 - methyl- 9#,10α-androst-4-en-3-one is prepared from 3- ethoxy - 17# - acetoxy - 18 - methyl - 9#,10α - androsta - 3,5 - diene via 6# - trichloromethyl- 17# - acetoxy - 18 - methyl - 9#,10α - androst - 4- en-3-one. 6 - Dibromomethylene - 17# - acetoxy - 18- methyl - 9#,10α - androst - 4 - en - 3 - one is prepared from 3-ethoxy-17#-acetoxy-18-methyl- 9#, 10α-androsta-3,5-diene via 6#-tribromomethyl- 17# - acetoxy - 18 - methyl - 9#,10α - androst - 4- en-3-one. 6# - Bromo - 6# - fluoro - 17# - acetoxy - 18 - methyl - 9#,10α - androst - 4 - en - 3 - one is prepared from 3-ethoxy-6-fluoro-17#-acetoxy-18- methyl - 9#,10α - androsta - 3,5 - diene by reaction with N-bromosuccinimide. Compounds of Formula I are stated to possess progestational, anabolic, antiestrogenic and antiandrogenic activities and to influence the secretion of gonadotropic hormones, and may be made up with carriers into pharmaceutical compositions for oral and parenteral administration.