| 摘要 |
<p>Copper-bromide mediated aromatization of 19-nor-androst-4-en-3-one compounds (II) to estra-1,3,5(10)-triene compounds (I) and their enantiomers or diastereomers in the presence of at least an electron-rich unsaturated organic additive (III), is claimed. Copper-bromide mediated aromatization of 19-nor-androst-4-en-3-one compounds of formula (II) to estra-1,3,5(10)-triene compounds of formula (I) and their enantiomers or diastereomers in the presence of at least an electron-rich unsaturated organic additive of formula (C(R 1>)(R 3>)=C(R 2>)(R 4>)) (III), is claimed. R : chemically stable residue; either R 1>, R 2>H, 1-6C-alkyl, 2-6C-alkenyl, 1-6C-alkoxy, 2-6C-alkeneoxy, 6C-aryl ring or 6C-aryloxy ring; or R 1>R 2>C : 6C aromate (optionally substituted by one or more OH, 1-6C-alkoxy and/or 1-6C-alkyl, 3-7C-cycloalkene or a monocyclic heteroaromate) or an unsaturated heterocycle (optionally, additionally substituted by R 3>or R 4>); and R 3>, R 4>H (optional), 1-6C-alkyl, 2-6C-alkenyl, 1-6C-alkoxy, 2-6C-alkeneoxy, 6C-aryl ring or 6C-aryloxy ring. Provided that: at least a residue of R 1>-R 4>is not H. INDEPENDENT CLAIMS are included for: (1) the preparations of (S)-7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthrene-3,17-diol compound of formula (VI) comprising (a) aromatization of halo substituted 19-nor-androst-4-en-3-one compounds of formula (IIb) to halo substituted estra-1,3,5(10)-triene compound of formula (Ib); (b) reaction of (Ib) with an amine compound of formula (H-W 1>-X-Y 1>-Z-E) (IV) to obtain amine substituted 3-hydroxy-6,7,8,9,11,12,13, 14,15,16-decahydro-cyclopenta[a]phenanthren-17-one compound of formula (V) and (c) nucleophilic alkylation of keto group of (V) at position 17, or carrying out steps (a), (c) and (b); and (2) the preparations of (11S,17S)-11-fluoro-7,8,9,11,12,13,14,15,16, 17-decahydro-6H-cyclopenta[a]phenanthrene-3,17-diol compound of formula (VIa) comprising (a1) aromatization of (S)-11-fluoro-1,6,7,8,9,10,11,12,13,14,15,16-dodecahydro-2H-cyclopent a[a]phenanthrene-3,17-dione compounds of formula (IIc) to (S)-11-fluoro-3-hydroxy-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopent a[a]phenanthren-17-one compound of formula (Ic), (b1) reaction of (Ic) with an alpha -alkyl(amine)-omega -perfluoro(alkyl)-alkane of formula (NH(R 7>-(CH 2) j-C mF 2 m + 1)) (IV) to obtain amine group substituted (S)-11-fluoro-3-hydroxy-6,7,8,9,11,12,13,14,15,16-decahyd ro-cyclopenta[a]phenanthren-17-one compound of formula (Va) and (c1) nucleophilic methylation of keto group of (Va) at position 17, or carrying out the steps of (a1), (c1) and (b1). Hal 2>F or Cl, which is bonded to estratriene group in 11beta -position; either R7a : OR1c, where R7a is bonded to estratriene group in 17beta -position; and R7b : 1-4C-alkyl or at least a partially fluorinated 1-4C-alkyl, where R7b is bonded to estratriene group in 17alpha -position; or R7aR7b : a keto group; R 6>3-11C-alkyl, which is bonded to estratriene at 7alpha -position; Hal 1>Cl, Br or I; either R8a : OR1d; and R8b : CH 3; or R8aR8b : a keto group; R1b, R1c, R1d : H or a protective group; i : 3-13; Hal : Cl, Br or I; W 1>N(R 7>); R 7>H or 1-4C-alkyl; X : (CH 2) q; q : 0-12; Y 1>a direct bond between X and Z or a SO ngroup; n : 0-2; Z : 1-7C-alkylene, which is at least partially fluorinated; E : CF 3or pentafluorophenyl; Hal : Cl, Br or I; j : 1-10; and m : 1-5. [Image] [Image] [Image] [Image]</p> |
