Patent GB-1147802-A (GB)
Title: Improvements in or relating to novel steroids and the manufacture thereof
IPC: C07J1/00
Filed: 1966-04-06
Abstract: 1,147,802. Steroids. UPJOHN CO. 6 April, 1966 [7 April, 1965], No. 52674/68. Divided out of 1,147,801. Heading C2U. The invention comprises novel compounds of the formula wherein Q represents hydrogen, methyl, C#CA, CH=CHCA or CH 2 CH 2 A, the 4,5 carbon atom linkage is a single or double bond, with the proviso that the 5-hydrogen atom is absent when the 4,5 carbon atom linkage is a double bond; R 1  and R 2  represent hydrogen or methyl, R 4  is a lower alkyl radical containing one to twelve carbon atoms, inclusive; A represents hydrogen, lower alkyl of from one to twelve carbon atoms, inclusive, chlorine, bromine or trifluoromethyl; Y<SP>11</SP> is a thioketal radical of the formula wherein n is one or two and R is hydrogen, or lower alkyl containing 1 to 6 carbon atoms inclusive or Y<SP>1</SP> where Y<SP>1</SP> represent and wherein Z is hydrogen, lower alkyl having from 1 to 12 carbon atoms inclusive or the lower acyl radical of an organic carboxylic acid containing from 1 to 12 carbon atoms inclusive and Z<SP>1</SP> is selected from the same radicals as Z or tetrahydropyranyl; and processes for the preparation of (1) compounds of the formula wherein R, R 1 , R 2 , Y<SP>1</SP> and Z<SP>1</SP> have the same meaning as above and Z represents hydrogen or the lower acyl radical of a carboxylic acid containing 1 to 12 carbon atoms inclusive; which comprises condensing compounds of the formula wherein R, R 1 , R 2 , Y<SP>1</SP> and Z have the same meanings as above by treatment with a formaldehyde of the formula (HCHO) n , wherein n is an integer and a thiol of the formula R<SP>1</SP>SH, wherein, R<SP>1</SP> is an alkyl or aryl radical containing one to twelve carbon atoms inclusive, in the presence of a catalyst to yield the corresponding 4-organothiomethyl compound of the formula wherein R, R<SP>1</SP>, R 1 , R 2 , Y<SP>1</SP> and Z have the same meaning as above which is then desulphurized by treatment with Raney nickel. (2) Compounds of the invention claimed in which Q is C#CA and Y<SP>11</SP> is Y<SP>1</SP>, which comprises alkynylating at the 17α position a corresponding compound of the formula wherein 4, 5, R 1 , R 2  and Y<SP>1</SP> have the same meaning as above, Y<SP>111</SP> represents (1) an alkylene ketal radical wherein n is one or two and R represents hydrogen or a lower alkyl radical containing from one to six carbon atoms, inclusive, (2) either wherein Z<SP>1</SP> has the same meaning as above and when Y<SP>111</SP> is (1) above; and then hydrolysing at the 3-position to yield the corresponding compound wherein Y<SP>111</SP> is (3) Compounds of the invention claimed in which Q is C#CA and Y<SP>11</SP> is carbonyl which comprises subjecting to alkynylation at the 17α-position a corresponding compound of the formula wherein R 1  and R 2  have the same meaning as above, the 5, 6 carbon atom linkage is a single or double bond with the proviso that the 5-hydrogen atom is absent when the 5,6-carbon atom linkage is a double bond and R is selected from alkyl of from one to five carbon atoms, inclusive, and a cyclic amino radical of the formula wherein n is four or five; and hydrolysing the 17α-compound at the 3-position to yield the corresponding 3-keto compound. Pharmaceutical compositions of the above compounds having anti-fertility, anti-androgenic and anti-estrogenic activities are administered orally or parenterally.