Japanese Patent JPS50105662

A

1330563 1#,2# - Methylene - 9#,10α - steroids PHILIPS GLOEILAMPENFABRIEKEN NV 19 April 1971 [4 March 1970] 22847/71 Heading C2U [Also in Division A5] The invention comprises compounds of formula wherein X is H and Y is free or esterified hydroxy, or X+Y is oxo; R 3 is a 3-oxo-#4, 3- oxo-#4,6, 3-OR1-#3,5, 3α-OR1-#4,6 or 3#-OR1- #4,6 system (where OR1 is an esterified or etherified hydroxy group); R 6 is H, Cl, F, Me, 6,6-difluoro or 6,6-dichloro 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 a 6#,7#- methylene group then R 6 is H, F or Cl and R 3 is a 3-oxo-#4 system; R 13 is Me or Et; R 17 is C 1-5 etherified hydroxy or C 1-8 esterified hydroxy; and R 21 is H, F or free or esterified hydroxy. Compounds I are prepared (i) by esterifying or etherifying the corresponding 17α-(free hydroxy) compounds (wherein R 3 is 3-oxo-#4 or 3-oxo-#4,6); (ii) by esterifying or etherifying the corresponding 3-(free hydroxy)-#4,6 compounds; (iii) by halogenating the corresponding #3,5-3- OR1-6-unsubstituted compounds to give #4-3- oxo-6-(fluoro or chloro) compounds; (iv) by converting the corresponding 21-iodo compounds (wherein R 3 is 3-oxo-#4) either into 21- fluoro compounds using AgF preferably in the presence of CaF 2 , or into 21-acetoxy compounds using triethylaminoacetic acid and an alkali metal acetate; (v) by catalytic hydrogenation of the corresponding 6-methylene, 6-dichloromethylene or 6-dibromomethylene compounds (wherein R 3 is 3-oxo-#4) into 6-methyl compounds ; (vi) by isomerization of the corresponding #4-3-oxo-6-methylene compounds into #4,6- 3-oxo-6-methyl compounds under palladium catalysis; and (vii) by dehydration of the corresponding #4-3-oxo-6-halo-7-hydroxy compounds into #4,6-3-oxo-6-halo compounds. Compounds I are interconverted by (i) 20/21- esterification/de-esterification; (ii) 3-enol esterification/enol etherification; (iii) reduction of 20-oxo to hydroxy; (iv) 6,7-hydrogenation/ dehydrogenation; (v) 6-dihalogenation; and (vi) 6,7-methylenation. 1#,2# - Methylene - 6# - chloro - 7# - hydroxy- 17α - acetoxy - 9#,10α - pregn - 4 - ene - 3,20 - dione is prepared from 1#,2# - methylene - 17α - acetoxy - 9#,10α - pregna - 4,6 - diene - 3,20 - dione by reaction with chromyl chloride. 1#,2#; 6#,7# - Bismethylene - 6α - chloro - 17α- hydroxy - 9#,10α - pregn - 4 - ene - 3,20 - dione is prepared from 1#,2#-methylene-6-chloro-17α- acetoxy - 9#,10α - pregna - 4,6 - diene - 3,20- dione via 1#,2# - methylene - 6 - chloro - 17α- hydroxy - 9#,10α - pregna - 4,6 - diene - 3,20- dione. 1#,2# - Methylene - 6 - methyl - 17α -hydroxy - 9#, 10α - pregna - 4,6 - diene - 3,20 - dione (1V) is prepared from 17α - hydroxy - 9#,10α - pregna: 1,4,6,triene-3,20-dione (I) by the sequence, I -# 1#,2# - methylene - 17α - hydroxy - 9#- 10α - pregna - 4,6 - diene - 3,20 - dione (II) -# 1#,2# - methylene - 17α - hydroxy - 9#,10α - pregn- 4 - ene - 3,20 - dione (III) -# 1#,2# - methylene- 6# - trichloromethyl - 17α - hydroxy - 9#,10α- pregn-4-ene - 3,20 - dione -# 1#,2#; 6 - bismethylene - 17α - hydroxy - 9#,10α - pregn - 4 - ene- 3,20-dione -# IV. 1#,2#; 6#,7# - Bismethylene - 17α - hydroxy- 9#,10α - pregn - 4 - ene - 3,20 - dione is prepared from II by reaction with dimethylsulphoxonium methylide. 1#,2# - Methylene - 3,17α - diacetoxy - 9#,10α- pregna-3,5-dien-20-one is prepared from III by reaction with Ac 2 O. 1#,2# - Methylene - 6 - fluoro - 17α - hydroxy- 9#,10α - pregna - 4,6 - diene - 3,20 - dione is prepared by hydrolysis of the 17-acetate thereof. 1#,2# - Methylene - 3α - hydroxy - 6 - chloro- 17α - acetoxy - 9#,10α - pregna - 4,6 - dien - 20- one is prepared by NaBH 4 reduction of the corresponding 3,20-dione.

JP14336774A

August 20, 1975

December 13, 1974

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C07J53/00; A61K9/00; A61K31/57; C07J5/00; C07J15/00; A61K; C07C; (IPC1-7): A61K31/57; C07J5/00

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