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US 4,052,421 AGranted
13-Ethinyl-steroids and processes for their manufacture
AssigneeCiba-Geigy Corporation
InventorsMichel Biollaz, Jaroslav Kalvoda
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AssigneeCiba-Geigy Corporation
InventorsMichel Biollaz, Jaroslav Kalvoda
Estimating the term…
A new class of 13-ethinyl-steroids is prepared by a novel process comprising Wittig reaction of a 13-formyl steroid with a chloro- or bromomethylenephosphorane and dehydrohalogenation of the intermediate 13-(2-halogenovinyl)steroid with an extremely strong base. Preferred products are those of the formula ##STR1## wherein R denotes a hydrogen atom or the methyl group, R.sub.3 denotes a hydrogen atom or a lower alkyl or lower alkanoyl group, R.sub.4 denotes a hydrogen atom or a lower aliphatic hydrocarbon radical, or R.sub.3 and R.sub.4 together denote a C--O linkage, R.sub.5 denotes the oxo group, a hydrogen atom together with an esterified or free hydroxyl group, or two hydrogen atoms, R.sub.6 denotes a hydrogen atom or a lower alkyl group, and R.sub.7 denotes a hydrogen atom or the methyl group, it also being possible for an additional 1,2-double bond to be present in compounds in which R is the methyl group. These compounds are pharmacologically active in a manner analogous to that of natural sexual hormones, and are distinguished as blockers of the secretion of pituitary gonadotrophins; accordingly, they are useful in medicine for the corresponding indications and for fertility control.
Process for the manufacture of 13-ethinyl-steroids of the general formula I ##STR12## wherein St denotes the remaining part of a steroid compound, and R.sub.1 denotes a member of the group consisting of a free oxo group, a ketalised oxo group, a free, etherified or esterified hydroxyl group together with a hydrogen atom, a free, etherified or esterified hydroxyl group together with a lower aliphatic hydrocarbon radical, and a free, etherified or esterified hydroxyl group together with a halogenated lower aliphatic hydrocarbon radical, characterised in that a corresponding 13-formyl-steroid of the general formula II ##STR13## wherein St.sub.a denotes a radical which corresponds to the radical St characterised above and in which, apart from the 11-oxo group, there are no free oxo groups, and R.sub.1a denotes a radical which corresponds to the radical R.sub.1 characterised above and in which no free oxo group is present, is subjected to a Wittig reaction with a bromomethylenephosphorane or chloromethylenephosphorane compound which carries three further hydrocarbon radicals on the phosphorus atom, and a resulting 13-(2-halogenovinyl) compound is dehydrohalogenated by means of an extremely strong base selected from the group consisting of potassium tert.-butylate in a polar solvent, an alkali metal amide in ammonia and an organometallic compound derived from an alkali metal.
13-Ethinyl-steroids of the general formula ##STR14## wherein R.sub.3 denotes a hydrogen atom or a lower alkyl or lower alkanoyl group, R.sub.4 denotes a hydrogen atom or a lower aliphatic hydrocarbon radical, or OR.sub.3 and R.sub.4 together denote an oxo group, and St represents a residue selected from a group consisting of residues of the partial formulae ##STR15## wherein R and R.sub.7 each denotes a hydrogen atom or the methyl group, R.sub.5 denotes an oxo group, a hydrogen atom together with a free hydroxyl group, a hydrogen atom together with an esterified hydroxyl group, or two hydrogen atoms, and R.sub.6 denotes a hydrogen atom or a lower alkyl group.
Dependencies are inferred from the claim text.