Patent GB-740568-A (GB)
Title: Steroid enamines
IPC: C07J75/00
Filed: 1953-04-30
Abstract: The invention comprises: (a) 3-tertiaryaminosteroids wherein ring A of the nucleus is non-aromatic but contains a double bond attached to the 3-carbon atom and wherein the tertiary amino group is a dialkylamino, dialkanolamino, dicycloalkylamino, aralkylalkylamino or arylalkylamino radical or a cyclic amino radical of a saturated monocyclic heterocyclic radical containing 5 or 6 ring members; (b) the production of such compounds by reacting a 3-ketosteroid with the appropriate secondary amine; and (c) a process for the production of a 3-ketosteroid alcohol by applying the process of (b) to a polycarbonyl steroid containing a 3-keto group (which reacts selectively with the secondary amine), reducing a keto group at a position other than 3 with lithium aluminium hydride, and then regenerating the 3-keto group by acid hydrolysis of the resulting 3-tertiary-aminosteroid alcohol in an aqueous inert organic solvent in which it is soluble.  Other substituents which may be present in the starting materials (e.g. in 7-, 11-, 12- or 17-positions) are, for example, hydroxy, acyloxy or carbalkoxy groups, or any of the natural side-chains in the 17-position, whilst the nucleus may also contain double bonds, which may or may not be conjugated with one another or with the 3-keto linkage (any 4(5) double bond shifting during the reaction to the 5(6)-position).  The process of (b) is preferably effected by heating the reactants (e.g. to about 40-110 DEG  C.) in an inert organic solvent, if desired in the presence of an acid dehydration catalyst (e.g. p-toluenesulphonic acid), and continuously removing the water formed.  The product thereof contains a 3(4)-double bond when the starting material has the normal configuration at C5, but 3-ketoallosteroids yield a mixture of compounds with 2(3) and 3(4) double bonds.  In examples, pyrrolidine is reacted with: (1) 4-cholesten-3-one to produce 3 - (N - pyrrolidyl) - 3:5 - cholestadiene; (2) stigmastadienone to produce 3-(N-pyrrolidyl)-3:5:22 - stigmastatriene; (3) cholestan - 3 - one to produce 3-(N-pyrrolidyl)-2- and -3-cholestene; (4) progesterone to produce 3-(N-pyrrolidyl) - 3:5 - pregnadien - 20 - one; (5) and (6) 11a - and 11b -hydroxyprogesterone to produce 3 - (N - pyrrolidyl) - 3:5 - pregnadien - 11a - and 11b -ol-20-one; (7) 11-ketoprogesterone to produce 3 - (N - pyrrolidyl) - 3:5 - pregnadien - 11:20 - dione; (8) methyl 3:7:12-triketocholanate to produce methyl 3-(N-pyrrolidyl) - 7:12 - diketo - 2- and - 3 - cholenate; (9) 11a -hydroxy-4-androstene-3:17-dione to produce 3 - (N - pyrrolidyl) - 3:5 - androstadien - 11a  - ol - 17 - one; (10) adrenosterone to produce 3 - (N - pyrrolidyl) - 3:5 - androstadiene - 11:17 - dione; (11) methyltestosterone to produce 3-(N-pyrrolidyl)-17-methyl-3:5-androstadien - 17 - ol; (12) 4 - androstene - 3:17 - dione to produce 3-(N-pyrrolidyl)-3:5 - androstadien-17-one.  In further examples: (13) the product of (12) is reduced with lithium aluminium hydride in ether to 3-(N-pyrrolidyl)-3:5 - androstadien - 17b  - ol (also obtainable from testosterone and pyrrolidine); (14) the product of (13) is refluxed with an aqueous methanolic solution of sodium acetate and hydrochloric acid to give testosterone.  The processes of (13) and (14) may be similarly applied to the products of (5) and (10), yielding respectively 11a :20 - dihydroxy - 4 - pregnen - 3-one and 11b -hydroxytestosterone.  Lists of additional starting materials and products are given.