Title:
METHODS OF ASYMMETRICALLY SYNTHESIZING ENANTIOMERS OF CASODEX, ITS DERIVATIVES AND INTERMEDIATES THEREOF
Document Type and Number:
WIPO Patent Application WO2001028990
Kind Code:
A3
Abstract:
A method of synthesizing pure enantiomers of acylanalides such as Casodex3 (bicalutamide) and its derivatives includes contacting a compound having a ring structure that, when opened, provides a substituent having the structure of Formula (I), with a compound having a structure of the Formula (II): R<7>-R<6>-X<1>H, under conditions sufficient to provide a compound having the structure of Formula (III) wherein X<2> is oxygen, sulfur, sulphinyl (-SO-), sulphonyl (-SO2-), imino (-NH-), oxidized imino alkylimino (-NR<8>-) where R<8> is alkyl having up to 6 carbon atoms, or oxidized alkylimino. The method further includes treating the compound of Formula (III) under conditions sufficient to provide a pure enantiomer of acylanalides such as Casodex3 (bicalutamide) and/or derivatives thereof. In preferred embodiments, R<1> is methyl, R<2> is methylene, R<6> is a direct link, R<7> is 4-fluorophenyl, X<1> is sulfur, the compound of Formula (II) is 4-fluorobenzenethiol, and X<2> is sulphonyl. Methods of synthesizing acylanalides such as Casodex3 (bicalutamide) and/or derivatives thereof from a starting material of citramalic acid are also provided.
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Inventors:
EKWURIBE NNOCHIRI (US)
Application Number:
PCT/US2000/041233
Publication Date:
September 07, 2001
Filing Date:
October 18, 2000
Export Citation:
Assignee:
NOBEX CORP (US)
EKWURIBE NNOCHIRI (US)
EKWURIBE NNOCHIRI (US)
International Classes:
C07B53/00; C07C315/02; C07C317/46; C07C319/14; C07C319/20; C07C323/60; C07D317/34; C07D498/04; C07C323/52; (IPC1-7): C07C317/34; C07C319/14; C07C323/52; C07C319/20; C07C323/60; C07C315/02; C07C317/46; C07M7/00
Other References:
H. TUCKER, ET AL.: "Resolution of the nonsteroidal antiandrogen 4'-cyano- 3-[(4-fluorophenyl)sulphonyl-2-hydroxy- 2-methyl-3'-(trifluoromethyl)- propionanilide and the determinatoin of the absolute configuration of the active enantiomer", JOURNAL OF MEDICINAL CHEMISTRY, vol. 31, no. 4, 1 April 1988 (1988-04-01), American Chemical Society, Washington, DC, US, pages 885 - 887, XP000605163, ISSN: 0022-2623
H. TUCKER, ET AL.: "Nonsteroidal antiandrogens. Synthesis and structure-activity relationships of 3-substituted derivatives of 2-hydroxypropionanilides", JOURNAL OF MEDICINAL CHEMISTRY, vol. 31, no. 5, 1 May 1988 (1988-05-01), American Chemical Society, Washington, DC, US, pages 954 - 959, XP000605264, ISSN: 0022-2623
H. EGGERER, ET AL.: "Synthese von Citramalyl-coenzym-A und Nachweis seiner enzymatischen Aldolspaltung", BIOCHEMISCHE ZEITSCHRIFT., vol. 342, no. 1, 1965, Springer, Berlin, DE, pages 40 - 53, XP000990449, ISSN: 0366-0753
M. FARINES, ET AL.: "Etude de dioxolanones-4: synthèse et propriétés physiques", BULLETIN DE LA SOCIETE CHIMIQUE DE FRANCE, no. 1, January 1970 (1970-01-01), Société française de chimie, Paris, FR, pages 332 - 340, XP002163440, ISSN: 0037-8968
D.H.R. BARTON, ET AL.: "A practical alternative to the Hunsdieker reaction", TETRAHEDRON LETTERS, vol. 24, no. 45, 1983, Elsevier Science Publishers, Amsterdam, NL, pages 4979 - 4982, XP002163441, ISSN: 0040-4039
A.L.J. BECKWITH, ET AL.: "Some diastereoselective radical reactions of substituted 1,3-dioxolan-4-ones", TETRAHEDRON, vol. 49, no. 36, 3 September 1993 (1993-09-03), Elsevier Science Publishers, Amsterdam, NL, pages 7871 - 7882, XP002163348, ISSN: 0040-4020
F. ZEUNER, ET AL.: "Synthese und Polymerisation von 2-Aryl-5-methylen-1,3-dioxolan-4-onen und Arylbis-(5-methylen-1,3-dioxolan-2-yl-4- on)en", JOURNAL FÜR PRAKTISCHE CHEMIE, CHEMIKER ZEITUNG, vol. 337, no. 6, 1995, Wiley VCH, Weinheim, DE, pages 478 - 485, XP002163349, ISSN: 1436-9966
R.P. HOF, ET AL.: "Synthesis and lipase-catalysed resolution of 5-(hydroxymethyl)-1,3-dioxolan-4-ones: masked glycerol analogues as potential building blocks for pharmaceuticals", JOURNAL OF ORGANIC CHEMISTRY, vol. 61, no. 10, 17 May 1996 (1996-05-17), American Chemical Society, Washington, DC, US, pages 3423 - 3427, XP002163350, ISSN: 0022-3263
H. TUCKER, ET AL.: "Nonsteroidal antiandrogens. Synthesis and structure-activity relationships of 3-substituted derivatives of 2-hydroxypropionanilides", JOURNAL OF MEDICINAL CHEMISTRY, vol. 31, no. 5, 1 May 1988 (1988-05-01), American Chemical Society, Washington, DC, US, pages 954 - 959, XP000605264, ISSN: 0022-2623
H. EGGERER, ET AL.: "Synthese von Citramalyl-coenzym-A und Nachweis seiner enzymatischen Aldolspaltung", BIOCHEMISCHE ZEITSCHRIFT., vol. 342, no. 1, 1965, Springer, Berlin, DE, pages 40 - 53, XP000990449, ISSN: 0366-0753
M. FARINES, ET AL.: "Etude de dioxolanones-4: synthèse et propriétés physiques", BULLETIN DE LA SOCIETE CHIMIQUE DE FRANCE, no. 1, January 1970 (1970-01-01), Société française de chimie, Paris, FR, pages 332 - 340, XP002163440, ISSN: 0037-8968
D.H.R. BARTON, ET AL.: "A practical alternative to the Hunsdieker reaction", TETRAHEDRON LETTERS, vol. 24, no. 45, 1983, Elsevier Science Publishers, Amsterdam, NL, pages 4979 - 4982, XP002163441, ISSN: 0040-4039
A.L.J. BECKWITH, ET AL.: "Some diastereoselective radical reactions of substituted 1,3-dioxolan-4-ones", TETRAHEDRON, vol. 49, no. 36, 3 September 1993 (1993-09-03), Elsevier Science Publishers, Amsterdam, NL, pages 7871 - 7882, XP002163348, ISSN: 0040-4020
F. ZEUNER, ET AL.: "Synthese und Polymerisation von 2-Aryl-5-methylen-1,3-dioxolan-4-onen und Arylbis-(5-methylen-1,3-dioxolan-2-yl-4- on)en", JOURNAL FÜR PRAKTISCHE CHEMIE, CHEMIKER ZEITUNG, vol. 337, no. 6, 1995, Wiley VCH, Weinheim, DE, pages 478 - 485, XP002163349, ISSN: 1436-9966
R.P. HOF, ET AL.: "Synthesis and lipase-catalysed resolution of 5-(hydroxymethyl)-1,3-dioxolan-4-ones: masked glycerol analogues as potential building blocks for pharmaceuticals", JOURNAL OF ORGANIC CHEMISTRY, vol. 61, no. 10, 17 May 1996 (1996-05-17), American Chemical Society, Washington, DC, US, pages 3423 - 3427, XP002163350, ISSN: 0022-3263
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