| US 7,514,466 B2 | ||
| Purification of progesterone receptor modulators | ||
| Bogdan Kazimierz Wilk, New City, N.Y. (US); Arkadiy Zinoviy Rubezhov, West Nyack, N.Y. (US); Anthony Francis Hadfield, Ruskin, Fla. (US); and Jean Louise Helom, Hillsdale, N.J. (US) | ||
| Assigned to Wyeth, Madison, N.J. (US) | ||
| Filed on Apr. 25, 2005, as Appl. No. 11/113,730. | ||
| Claims priority of provisional application 60/565659, filed on Apr. 27, 2004. | ||
| Prior Publication US 2005/0250766 A1, Nov. 10, 2005 | ||
| Int. Cl. A01N 43/38 (2006.01); A61K 31/40 (2006.01) | ||
| U.S. Cl. 514—409 [514/414; 514/421] | 29 Claims |
1. A method for purifying a compound of formula I:
 A and B are joined to form a ring comprising (i), (ii), or (iii):
(i) a carbon-based 3 to 8 membered saturated spirocyclic ring;
(ii) a carbon-based 3 to 8 membered spirocyclic ring containing in its backbone one or more carbon-carbon double bonds; or
(iii) a 3 to 8 membered heterocyclic ring containing in its backbone one to three heteroatoms selected from the group consisting
of O, S and N;
the rings of (i), (ii) and (iii) being optionally substituted by from 1 to 4 groups selected from the group consisting of
fluorine, C1 to C6 alkyl, C1 to C6 alkoxy, C1 to C6 thioalkyl, CF3, OH, CN, NH2, NH(C1 to C6 alkyl), and N(C1 to C6 alkyl)2;
T is absent;
Q is O, S, or NR3;
R1 is (iv), (v), or (vi):
(iv) halogen;
(v) a substituted benzene ring containing the substituents X, Y and Z as shown below:
 X is selected from the group consisting of H, halogen, CN, C1 to C3 alkyl, substituted C1 to C3 alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 thioalkoxy, substituted C1 to C3 thioalkoxy, amino, C1 to C3 aminoalkyl, substituted C1 to C3 aminoalkyl, NO2, C1 to C3 perfluoroalkyl, 5 or 6 membered heterocyclic ring containing in its backbone 1 to 3 heteroatoms, SO2NH2, CORC, OCORC, and NRDCORC;
RC is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
RD is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
Y and Z are independently selected from the group consisting of H, halogen, CN, NO2, amino, aminoalkyl, C1 to C3 alkoxy, C1 to C3 alkyl, and C1 to C3 thioalkoxy; or
(vi) a five or six membered ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S,
SO, SO2 and NR2 and containing one or two substituents independently selected from the group consisting of H, halogen, CN, NO2, amino, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, SO2NH2, CORE, and NRFCORE;
RE is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
RF is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
R2 is H, absent, O, or C1 to C4 alkyl; and
R3 is C1 to C6 alkyl, substituted C1 to C6 alkyl, aryl, substituted aryl, CN, C(O)R4, SO2R4, SCN, OR4, SR4, C(O)OR4, C(S)OR4, C(O)SR4, or C(S)SR4;
R4 is C1 to C6 alkyl, substituted C1 to C6 alkyl, aryl, or substituted aryl;
wherein said method comprises:
(a) treating a sample of a compound of formula I which contains greater than about 1% by weight impurities with a base in
the presence of a solvent to form a basic salt; and
(b) converting said basic salt to a purified form of a compound of formula I by treating said basic salt with water, acid,
or heat.
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