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US 6,187,925 B1Granted
Intermediates and process for the synthesis of azasteroids
AssigneeMerck & Co., Inc.
InventorsGuy R. Humphrey, Ross A. Miller, Wenjie Li
Life of this patent
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Abstract
The novel process of this invention involves the stereoselective synthesis of certain 16-substituted 4-aza-5α-androst-1-en-3-ones, and the useful intermediates obtained therein.
Claims15
A process for producing a compound of structural formula (11):
- wherein:
- Ar is an unsubstituted or mono- or di-substituted phenyl, naphthyl,or 5, 6 or 7 membered heteroaromatic ring containing at least one member selected from the group consisting of:
- one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof;
- in which the heteroaromatic ring can also be fused with one benzo or heteroaromatic ring;
- produced by:
- treating a compound of structural formula (10):
- with potassium t-butoxide, and isolating the resulting product (11).
4 more elements
A process for producing a compound of structural formula (11):
- wherein:
- Ar is an unsubstituted or mono- or di-substituted phenyl, naphthyl,or 5, 6 or 7 membered heteroaromatic ring containing at least one member selected from the group consisting of:
- one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof;
- in which the heteroaromatic ring can also be fused with one benzo or heteroaromatic ring;
- comprising:
- (a) by treating a compound of structural formula (1):
- with methyl magnesium chloride in the presence of cerium chloride in an organic solvent to produce (2):
- (b) treating the compound of structural formula (2) with aluminum isopropoxide and 2-butanone in the presence of organic base in an organic solvent, followed by addition of aqueous acid to the solution, neutralization with aqueous base and isolation (3) as a solution in the organic solvent:
- (c) treating the compound of structural formula (3) with 10% Pd/C, cyclohexene, and ethanol in an organic solvent, and isolating the resulting product (4):
- (d) treating the compound of structural formula (4) with sodium periodate and catalytic potassium permanganate and sodium carbonate, and isolating the resulting product (5):
- (e) treating the compound of structural formula (5) with ammonium acetate in refluxing acetic acid, and isolating the resulting product (6):
- (f) treating the compound of structural formula (6) with lithium tri-sec-butylborohydride, followed by an oxidative workup, and and isolating the resulting product (7):
- (g) hydrogenating the compound of structural formula (7) and isolating the resulting product (8):
- (h) treating the compound of structural formula (8) with potassium t-butoxide, adding Ar-F, and isolating the resulting product (9):
- (i) treating the compound of structural formula (9) with trimethylsilyl chloride in the presence of an organic base and adding iodine, and isolating the resulting product (10):
- (i) treating the compound of structural formula (10) with potassium t-butoxide, and isolating the resulting product (11).
13 more elements
Dependencies are inferred from the claim text.