GB893142A - Improvements in or relating to steroids and the manufacture thereof - Google Patents

Improvements in or relating to steroids and the manufacture thereof

Info

Publication number
GB893142A
GB893142A GB16654/58A GB1665458A GB893142A GB 893142 A GB893142 A GB 893142A GB 16654/58 A GB16654/58 A GB 16654/58A GB 1665458 A GB1665458 A GB 1665458A GB 893142 A GB893142 A GB 893142A
Authority
GB
United Kingdom
Prior art keywords
alkyl
aryl
compound
hydroxy
treating
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB16654/58A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pharmacia and Upjohn Co
Original Assignee
Upjohn Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Upjohn Co filed Critical Upjohn Co
Publication of GB893142A publication Critical patent/GB893142A/en
Expired legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J1/00Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J75/00Processes for the preparation of steroids in general

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)

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.
GB16654/58A 1957-05-27 1958-05-23 Improvements in or relating to steroids and the manufacture thereof Expired GB893142A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US893142XA 1957-05-27 1957-05-27

Publications (1)

Publication Number Publication Date
GB893142A true GB893142A (en) 1962-04-04

Family

ID=22216947

Family Applications (1)

Application Number Title Priority Date Filing Date
GB16654/58A Expired GB893142A (en) 1957-05-27 1958-05-23 Improvements in or relating to steroids and the manufacture thereof

Country Status (1)

Country Link
GB (1) GB893142A (en)

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