Preparation of 4-aza-17-substituted-5.alpha.-androstan-3-ones useful as 5.alpha.-reductase inhibitors

Abstract

A method of preparing a compound of the formula: ##STR1## where Formula (I) may also have the structure of partial Formula (III); wherein, ##STR2## R' is hydrogen or methyl; R" is hydrogen or .beta.-methyl; R'" is .beta.-methyl or hydroxy; Z is (1) oxo; (2) .beta.-hydrogen and .alpha.-hydroxy; or .alpha.-hydrogen or .alpha.-hydroxyl and (3) (Y).sub.n Q where n=0 or 1, Y is a straight or branched hydrocarbon chain of 1 to 12 carbon atoms and Q is ##STR3## where R.sup.8 is, ##STR4## where the dashed bond replaces the 17.alpha. hydrogen; (6) cyano; or (7) tetrazolyl; and pharmaceutically acceptable salts of the above compounds; CHARACTERIZED IN THAT (I.) a compound of the formula: ##STR5## , where A has the meanings above except --CH.dbd.CH--, is (1) treated with an oxidizing agent at reduced temperatures to form the corresponding 5-oxo-3,5-seco-androstan-3-oic acid compound; (2) treating the product of step (1) with an amine of formula: R.sup.1 NH.sub.2 to form the corresponding 4-aza-5-androsten-3-one compound substituted in the 4-position with R.sup.1 ; and (3) treating the product of step (2) with hydrogen under catalytic conditions to form the compound of Formula I and I & II wherein B is ##STR6## (II.) and where it is desired to prepare compounds of Formula I wherein B is ##STR7## additionally carrying out the following steps on the products prepared by the procedures in (I.) above: (1) alkylating the lactim carbonyl by treating it with trialkyloxonium tetrafluoroborate to form the corresponding alkyl iminium ether, i.e., the compound of Formula I where B is as above and R.sup.4 =OR.sup.5 ; (2) treating the product of step (1) with an amine of formula HNR.sup.6 R.sup.7 followed by treatment with a mineral acid to form the compound of Formula I where B is as above and R.sup.4 =NR.sup.6 R.sup.7 ; (III.) and where it is desired to prepare compounds of Formula I wherein A is --CH.dbd.CH--, additionally carrying out the following steps on the products prepared by the procedures in (I.) above: (1) treating the 1,2 saturated compound with lithium diisopropyl amide to form the corresponding enolate; (2) treating the enolate of step (1) in situ with diphenyldisulfide to form the corresponding .alpha.-phenylthio compound; (3) oxidizing the product of step (2) to form the corresponding sulfoxide compound; and (4) heating the product of step (3) to form the compound of Formula I wherein A is --CH.dbd.CH--.

Dependencies are inferred from the claim text.