Patent GB-893142-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
IPC: C07J1/00
Filed: 1958-05-23
Abstract: The invention comprises compounds of the general formula <FORM:0893142/IV (b)/1> wherein R1 represents hydrogen or the acyl group derived from a hydrocarbon carboxylic acid containing from 1 to 8 carbon atoms, R11 represents an alkyl or aryl radical, R111 represents a b -hydroxy or keto group and X represents hydrogen, chlorine, bromine or fluorine, and the preparation of such compounds wherein X represents hydrogen by treating a 5a , 11b  - dihydroxy - 6b  - alkyl (or aryl) andros - tane-3,17-dione with a cyclic secondary amine of the general formula <FORM:0893142/IV (b)/2> wherein n and n1 represent 1 or 2, to form a 3 - (N - cyclic tertiaryamino) - 6 - alkyl (or aryl) - 11b  - hydroxy - 3, 5 - androstadien - 17 - one, treating this compound with an alkyl or aryl Grignard reagent and then hydrolysing the thus obtained 3 - (N - cyclic tertiaryamino) - 6 - alkyl (or aryl)-17a -alkyl (or aryl)-11b ,17b -dihydroxy-3,5-androstadiene with a base to form 6a -alkyl (or aryl)-17a -alkyl (or aryl)-11b -hydroxy-testosterone and, if desired, oxidising this compound to form 6a -alkyl (or aryl)-17a -alkyl (or aryl)-11-keto-testerone.  This process may be modified in that the starting compound is prepared by treating 11b  - hydroxy - 5 - androstene - 3, 17 - dione - 3, 17 - bis (alkylene ketal) with a per - acid to obtain the corresponding 5,6-oxido-11b -hydroxy - androstane - 3, 17 - dione 3, 17 - bis (alkylene ketal), reacting this compound with a metal alkylating or arylating agent, and then hydrolysing the resulting 5a ,11b -dihydroxy-6b -alkyl (or aryl)-androstane-3,17-bis(alkylene ketal) with an acid.  The invention also includes a process for the preparation of compounds of the general formula <FORM:0893142/IV (b)/3> wherein R1 represents hydrogen or the acyl group of a hydrocarbon carboxylic acid containing 1 to 8 carbon atoms and R11 represents an alkyl or aryl group, by treating the corresponding 11b -hydroxy compound having a saturated 9(11) bond with N-bromoacetamide in pyridine and then with sulphur dioxide, a process for the preparation of compounds of the general formula <FORM:0893142/IV (b)/4> wherein R1 and R11 have the above significance, by treating a compound of the general formula <FORM:0893142/IV (b)/5> wherein R1 and R11 have the above significance and Y represents bromine or chlorine, with potassium acetate with the optional further step of treating the 9,11-oxido compound with hydrogen fluoride to produce a 6a -alkyl (or aryl)-17a - alkyl (or aryl) - 9a  - fluoro - 11b , 17b  - dihydroxy-4-androsten-3-one and, if desired, oxidising this compound with chromic anhydride in acetic acid to produce the corresponding 11-keto compound; and a process for the preparation of a compound of the first general formula above wherein X represents chlorine or bromine by treating 6a -alkyl (or aryl)-17a -alkyl (or aryl)-11b -hydroxy-testerone in pyridine with N-bromoacetamide and then with sulphur dioxide, reacting the resulting 6a -alkyl (or aryl)-17a -alkyl (or aryl)-17b -hydroxy-4,9(11)-androstadien-3-one with N-bromo- or N-chloro-acetamide in the presence of perchloric acid to form a 6a -alkyl (or aryl)-17a -alkyl (or aryl)-9a -bromo (or chloro)-11b ,17a -dihydroxy-4-androsten-3-one and, if desired, oxidising this compound to produce the corresponding 11-keto compound.  Detailed examples are given.  5a , 11b  - Dihydroxy - 6b - alkyl (or aryl) - androstane-3,17-dione is prepared by heating 11b - hydroxy - 4 - androstene - 3, 17 - dione with an alkylene glycol to form 3,17-bis(alkylene ketal) of 11b -hydroxy-4-androstene-3,17-dione, treating this compound with a per-acid to form the corresponding 5a ,6a -oxido compound, treating this compound with a metal alkylating or arylating agent to form a 5a ,11b -dihydroxy-6b -alkyl (or aryl)-androstane-3,17-dione 3,17-bis-(alkylene ketal), and hydrolysing the last mentioned compound.ALSO:A pharmaceutical composition contains as the active ingredient a steroid compound of the formula <FORM:0893142/VI/1> wherein R1 represents hydrogen or the acyl radical of a hydrocarbon carboxylic acid containing 1 to 8 carbon atoms, R11 represents an alkyl or aryl radical, R111 represents a b -hydroxy or keto radical, and X represents hydrogen, chlorine, bromine or fluorine, and a pharmaceutically acceptable carrier.  The composition is suitable for administration by injection-particularly as a suspension in oil or aqueous vehicles.  6a ,17a  - Dimethyl- 11b  - hydroxytestosterone or 6a , 17a -Dimethyl-11-ketotestosterone may also be used in oral preparations as tablets together with hexyl barbital sodium.