| US 7,482,449 B2 | ||
| Process for making spirolactone compounds | ||
| Ralph P. Volante, Cranbury, N.J. (US); David M. Tschaen, Holmdel, N.J. (US); Steven A. Weissman, Short Hills, N.J. (US); Matthew Heileman, New Providence, N.J. (US); Toshiaki Mase, Okazaki (Japan); Takehiko Iida, Okazaki (Japan); Kenji Maeda, Okazaki (Japan); Toshihiro Wada, Tsukuba (Japan); Hiroki Sato, Okazaki (Japan); and Kenichi Asakawa, Okazaki (Japan) | ||
| Assigned to Merck & Co., Inc., Rahway, N.J. (US); and Banyu Pharmaceutical Co., Ltd., (Japan) | ||
| Filed on Mar. 19, 2008, as Appl. No. 12/77,419. | ||
| Application 12/077419 is a division of application No. 10/531361, granted, now 7,368,569, previously published as PCT/US03/32393, filed on Oct. 14, 2003. | ||
| Claims priority of provisional application 60/419464, filed on Oct. 18, 2002. | ||
| Prior Publication US 2008/0171888 A1, Jul. 17, 2008 | ||
| Int. Cl. C07D 405/12 (2006.01); C07D 405/14 (2006.01); C07D 307/94 (2006.01); C07D 491/107 (2006.01) | ||
| U.S. Cl. 544—230 [544/231; 544/182; 544/332; 544/336; 546/5; 546/146; 548/311.4; 548/364.4; 549/265] | 32 Claims |
1. A process for preparing a compound of the formula IA, or a salt thereof,
 T, U, V and W are each independently selected from the group consisting of
(1) nitrogen, and
(2) methine,
wherein the methine group is unsubstituted or optionally substituted with a substituent selected from the group consisting
of
(a) halogen,
(b) lower alkyl,
(c) hydroxy, and
(d) lower alkoxy, and
wherein at least two of T, U, V, and W are methine;
comprising the steps of
(a) combining a strong base with a compound of formula A
 in an aprotic solvent to form a solution;
(b) reacting a compound of formula B
 wherein
wherein R2 is selected from the group consisting of:
(a) lower alkyl, and
(b) —CH2-phenyl, wherein the phenyl group is
unsubstituted or substituted with a substituent selected from the group consisting of
(1) lower alkyl,
(2) lower alkoxy, and
(3) —NO2,
with the solution of step (a) to form a solution;
(c) adjusting the pH of the solution of step (b) to between about 0 and 4 with an acid to form a compound of formula E
 (d) contacting the compound of formula F of step (c), wherein at least one of T, U, V and W is nitrogen, with an acid to form
a salt of compound E; and
(e) treating compound E, or a salt thereof, with an acid to form a salt of compound IA.
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