Patent GB-1336763-A (GB)
Title: 9beta, 10alpha-steroids their preparation and pharmaceutical preparations containing the same
IPC: C07J5/00
Filed: 1971-04-19
Abstract: 1336763 9#,10α-Steroids PHILIPS GLOEILAMPENFABRIEKEN NV 19 April 1971 [4 March 1970] 22846/71 Heading C2U [Also in Division A5] The invention comprises compounds of formula wherein R is a 3-oxo-#<SP>4</SP>, -#<SP>1,4</SP>, -#<SP>4,6</SP> or -#<SP>1,4,6</SP> group, a 1#,2#-methylene-3-oxo-#<SP>4</SP> or -#<SP>4,6</SP> group, a 3-OR-#<SP>3,5</SP> or -#<SP>4,6</SP> group, a 1#,2#- methylene-3-OR-#<SP>3,5</SP> or -#<SP>4,6</SP> group or a 3-OR<SP>1</SP>- #<SP>2,4,6</SP> group wherein OR is etherified or esterified hydroxy and OR<SP>1</SP> is esterified hydroxy; R 6  is H, Cl, F, Me, di-Cl or di-F, with the proviso that when R 6  is H then R 7  is 6#,7#-methylene; R 7  is a 7-hydrogen atom or a 6#,7#-methylene group, with the proviso that when R 7  is 6#,7#-methylene then R 6  is α-H, α-Cl or α-F and R is a 3-oxo- #<SP>4</SP>, 3-oxo-#<SP>1,4</SP> or 1#,2#-methylene-3-oxo-#<SP>4</SP> group; R 13  is Me or Et; R 17  is C 1-5  etherified hydroxy or C 1-7  esterified hydroxy; R 21  is H, F, OH or esterified hydroxy; X is H, Y is OH or esterified hydroxy, or X and Y together represent oxo. Preparations of compounds I.-(i) Catalytic acylation of #<SP>4</SP>-3-oxo-16#-methyl-16α,17α-epoxy compounds to give #<SP>4</SP>-3-oxo-16-methylene-17α- acyloxy products; (ii) 17-esterification or etherification of the corresponding free 17α-ols; (iii) 6,7-methylenation of corresponding 6-unsubstituted - #<SP>4,6</SP> compounds ; (iv) 3-esterification or etherification of corresponding 3- hydroxy-#<SP>4,6</SP> compounds; (v) conversion of corresponding 21-iodo compounds to 21-fluoro or 21-acetoxy products; (vi) dehydration of corresponding 6-chloro-7-hydroxy compounds to give 6-chloro-#<SP>6</SP> products; (vii) palladiumcatalysed isomerization of 6-methylene compounds to 6-methyl-#<SP>6</SP> products; (viii) 6-halogenation of a 3-(etherified or esterified hydroxy)- #<SP>3,5</SP>-6-unsubstituted compound to produce a 3-oxo-6-halo-#<SP>4</SP> product. Interconversions of compounds I.-(i) #<SP>1</SP>- and #<SP>6</SP>-dehydrogenation; (ii) hydrogenation of #<SP>4,6</SP> to #<SP>4</SP>; (iii) conversion of 6-monohalo to 6- dihalo; (iv) 6,7-methylenation; (v) 20- and 21- esterification; (vi) hydrolysis of 21-acyloxy; (vii) reduction of 20-oxo to 20-hydroxy; (viii) 3- enol-esterification and -etherification. 3,17α - Diacetoxy - 16 - methylene - 9#,10α- pregna-3,5-dien-20-one (XVI) is prepared from 9#,10α-pregna-4,6,16-triene-3,20-dione (X) by the sequence: X -# 9#,10α - pregna - 4,6- dieno[17α,16α]pyrazoline- 3,20 - dione (XI) -# 16 - methyl - 9#,10α - pregna - 4,6,16 - triene- 3,20 - dione (XII) -# 16# - methyl - 16α,17α- epoxy - 9#,10α - pregna - 4,6 - diene - 3,20 - dione (XIII) -# 16 - methylene - 17α - hydroxy- 9#,10α - pregna - 4,6 - diene - 3,20 - dione (XIV) -# 16 - methylene - 17α - acetoxy - 9#,10α- pregna - 4,6 - diene - 3,20 - dione (XV) -# 16 - methylene - 17α - acetoxy - 9#,10α - pregn - 4- ene-3,20-dione -# XVI. Alternatively XVI is prepared from 6,7-dihydro-X via the 6,7-dihydro analogues of XI, XII, XIII and XIV. 6# - Chloro - 7# - hydroxy - 16 - methylene - 17α- acetoxy - 9#,10α - pregn - 4 - ene - 3,20 - dione is prepared from XV with chromyl chloride. 6α - Chloro - 6#,7#; 16 - bismethylene - 17α- hydroxy 9#,10α - pregn - 4 - ene - 3,20 - dione is prepared from XII via 6#,7#; 16α,17α-diepoxy- 16# - methyl - 9#,10α - pregn - 4 - ene - 3,20 - dione and 6 - chloro - 16 - methylene - 17α - hydroxy- 9#,10α-pregna-4,6-diene-3,20-dione. 17α - Hydroxy - 1#,2#; 16 - bismethylene- 9#,10α-pregn-4-ene-3,20-dione is prepared from 17α - hydroxy - 16 - methylene - 9#,10α - pregna- 1,4,6-triene-3,20-dione via 17α-hydroxy-1#,2#; 16 - bismethylene - 9#,10α - pregna - 4,6 - diene- 3,20-dione. 6 - Fluoro - 16 - methylene - 17α - hydroxy- 9#,10α - pregna - 4,6 - diene - 3,20 - dione and 6 - (chloro or fluoro) - 17α - hydroxy - 1#,2#; 16- bismethylene - 9#,10α - pregna - 4,6 - diene - 3,20- dione are each prepared by hydrolysis of the respective 17-acetates thereof.