WO1994008986A1 - Enantiomeric cis-3-(4,6-dihydroxychroman-3-yl-methyl)benzoic acids - Google Patents
Enantiomeric cis-3-(4,6-dihydroxychroman-3-yl-methyl)benzoic acids Download PDFInfo
- Publication number
- WO1994008986A1 WO1994008986A1 PCT/US1993/006061 US9306061W WO9408986A1 WO 1994008986 A1 WO1994008986 A1 WO 1994008986A1 US 9306061 W US9306061 W US 9306061W WO 9408986 A1 WO9408986 A1 WO 9408986A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dihydroxychroman
- compound
- salt
- benzoic acid
- formula
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
Definitions
- This invention relates to c/s-3-(4,6-dihydroxychroman-3-ylmethyl)benzoic acids and processes for the preparation of such compounds.
- the compounds are intermediates useful in the preparation of optically pufe enantiomers of c/s-3-(6- arylmethyloxy-4-hydroxy-chroman-3-ylmethyl)aniline sulfonamides.
- the latter compounds are useful in the treatment of asthma, arthritis, psoriasis, ulcers, myocardial infarction and related diseases.
- the present invention relates to the compound of the formula
- the present invention also relates to the optically pure diasteriomeri salts of the compound of formula I with the compound of formula
- the compound of formula I is prepared, according to the invention, by acidifying the diasteriomeric salt of the compound of formula I with the compound of formula III.
- the diasteriomeric salt of the compound of formula I with the compound of formula III is prepared according to the invention, by treating the compound of formula
- the present invention also relates to a novel method for preparing the compound of formula II by reducing the compound of formula
- a reducing agent selected from diisobutylaluminum hydride and borohydride ion in the presence of Ce (III) ion.
- the compound of formula I also referred to herein as (3R-c/s)-3-(4,6- dihydroxychroman-3-ylmethyl)benzoic acid, is a novel compound prepared by acidifying the diasteriomeric salt of the compound of formula I and the compound of formula III in the presence of a solvent for the free acid.
- the acidification is effected using an acid with a pK a of about ⁇ 3 such as HCI, H 2 S0 4 , oxalic and citric acids.
- the diasteriomeric salt of the compound of formula I and the compound of formula III is prepared by heating the compounds of formulae II and III in the presence of a non-solvent for said salt and recovered, after cooling to room temperature, by filtration.
- Non-solvents for the diasteriomeric salt include ethanol and isopropanol.
- the preferred non-solvent is ethanol.
- the reaction is preferably carried out at a temperature between about 0°C and about 80°C, preferably at the reflux temperature of the non-solvent. Most preferably the reaction is effected at about 80°C.
- the treatment of the compound of formula II with the compound of formula III is carried out over a period of about 30 minutes to about 3 hours, preferably about 1 hour.
- the salt is purified by slurrying with the non-sumble at an elevated temperature followed by filtration at about room temperature.
- the slurrying procedure is, preferably, effected two times.
- the other cis enantiomer, i.e. (3S-c/s)-3-(4,6-dihydroxychroman-3- ylmethyl)benzoic acid may be prepared by substituting the (+) base for the compound of formula III.
- the 3S- acid may be prepared by treating the filtrate from the preparation of the diasteriomeric salt of the compound of formula I with acid followed by said (+ ) base followed by the above-indicated treatment for the salts with the (-) base.
- Racemic c/s-3-(4,6-dihydroxychroman-3-ylmethyl)benzoic acid (compound II) is prepared, according to the invention, by the novel process of treating the compound of formula IV with a solution of a reducing agent in tetrahydrofuran/methanol.
- a reducing agent in tetrahydrofuran/methanol.
- Preferred reducing agents are diisobutylaluminum hydride and borohydride in the presence of a Ce (III) salt.
- a most preferred reducing agent is borohydride ion in the presence of a Ce(lll) salt.
- the tetrahydrofuran and methanol may be present in a ratio of from about 3:1 to about 1 :2, preferably about 3:1.
- the reduction may be effected at a temperature from about -78°C to about 60°C, preferably at about 0°C.
- the sulfonamides, especially the trifluoromethanesulfonamides, of the compound of formula VI are useful in the treatment of asthma, arthritis, psoriasis, ulcers, myocardial infarction and related diseases.
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PL93308473A PL308473A1 (en) | 1992-10-21 | 1993-06-30 | Enabntiomeric cis-3-(4,6-dihydoxychroman-3-yl methyl)bezoic acids |
KR1019950701524A KR950704291A (en) | 1992-10-21 | 1993-06-30 | Enantiomeric cis-3- (4,6-dihydroxychroman-3-ylmethyl) benzoic acid (enantiomeric cis-3- (4,6-DIHYDROXYCHROMAN-3-YLMETHYL) BENZOIC ACIDS) |
AU46504/93A AU4650493A (en) | 1992-10-21 | 1993-06-30 | (Enantiomeric cis)-3-(4,6-dihydroxychroman-3-YL-methyl)benzoic acids |
EP93916752A EP0665839A1 (en) | 1992-10-21 | 1993-06-30 | $i(ENANTIOMERIC CIS)-3-(4,6-DIHYDROXYCHROMAN-3-YLMETHYL)BENZOIC ACIDS |
JP6509963A JPH07507811A (en) | 1992-10-21 | 1993-06-30 | Enantiomeric cis-3-(4,6-dihydroxychroman-3-yl-methyl)benzoic acid |
NO951507A NO951507L (en) | 1992-10-21 | 1995-04-20 | Enantiomeric cis-3- (4,6-dihydroxychromoman-3-yl-methyl) benzoic acids |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US96433692A | 1992-10-21 | 1992-10-21 | |
US07/964,336 | 1992-10-21 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1994008986A1 true WO1994008986A1 (en) | 1994-04-28 |
Family
ID=25508434
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1993/006061 WO1994008986A1 (en) | 1992-10-21 | 1993-06-30 | Enantiomeric cis-3-(4,6-dihydroxychroman-3-yl-methyl)benzoic acids |
Country Status (16)
Country | Link |
---|---|
EP (1) | EP0665839A1 (en) |
JP (1) | JPH07507811A (en) |
KR (1) | KR950704291A (en) |
CN (1) | CN1090577A (en) |
AU (1) | AU4650493A (en) |
CA (1) | CA2146005A1 (en) |
CZ (1) | CZ100895A3 (en) |
FI (1) | FI934624A (en) |
HU (1) | HUT65128A (en) |
IL (1) | IL107293A0 (en) |
MX (1) | MX9306526A (en) |
MY (1) | MY131378A (en) |
NO (1) | NO951507L (en) |
PL (1) | PL308473A1 (en) |
WO (1) | WO1994008986A1 (en) |
ZA (1) | ZA937737B (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998011085A1 (en) * | 1996-09-16 | 1998-03-19 | Pfizer Inc. | Processes and intermediates for preparing substituted chromanol derivatives |
WO2001034563A1 (en) * | 1999-10-27 | 2001-05-17 | Nobex Corporation | Resolution of intermediates in the synthesis of substantially pure bicalutamide |
US6479692B1 (en) | 2001-05-02 | 2002-11-12 | Nobex Corporation | Methods of synthesizing acylanilides including bicalutamide and derivatives thereof |
US6482848B2 (en) | 2000-05-24 | 2002-11-19 | Sugen Incorporated | Prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives |
US7601855B2 (en) | 2004-09-21 | 2009-10-13 | Novogen Research Pty Ltd | Substituted chroman derivatives, medicaments and use in therapy |
US8080675B2 (en) | 2004-09-21 | 2011-12-20 | Marshall Edwards, Inc. | Chroman derivatives, medicaments and use in therapy |
US9663484B2 (en) | 2010-11-01 | 2017-05-30 | Mei Pharma, Inc. | Isoflavonoid compounds and methods for the treatment of cancer |
US10980774B2 (en) | 2015-02-02 | 2021-04-20 | Mei Pharma, Inc. | Combination therapies |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5059609A (en) * | 1987-10-19 | 1991-10-22 | Pfizer Inc. | Substituted tetralins, chromans and related compounds in the treatment of asthma, arthritis and related diseases |
-
1993
- 1993-06-30 EP EP93916752A patent/EP0665839A1/en not_active Withdrawn
- 1993-06-30 CA CA002146005A patent/CA2146005A1/en not_active Abandoned
- 1993-06-30 CZ CZ951008A patent/CZ100895A3/en unknown
- 1993-06-30 WO PCT/US1993/006061 patent/WO1994008986A1/en not_active Application Discontinuation
- 1993-06-30 KR KR1019950701524A patent/KR950704291A/en not_active Application Discontinuation
- 1993-06-30 AU AU46504/93A patent/AU4650493A/en not_active Abandoned
- 1993-06-30 PL PL93308473A patent/PL308473A1/en unknown
- 1993-06-30 JP JP6509963A patent/JPH07507811A/en active Pending
- 1993-10-14 IL IL107293A patent/IL107293A0/en unknown
- 1993-10-19 ZA ZA937737A patent/ZA937737B/en unknown
- 1993-10-20 CN CN93119050A patent/CN1090577A/en active Pending
- 1993-10-20 MY MYPI93002174A patent/MY131378A/en unknown
- 1993-10-20 MX MX9306526A patent/MX9306526A/en unknown
- 1993-10-20 HU HU9302973A patent/HUT65128A/en unknown
- 1993-10-20 FI FI934624A patent/FI934624A/en not_active Application Discontinuation
-
1995
- 1995-04-20 NO NO951507A patent/NO951507L/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5059609A (en) * | 1987-10-19 | 1991-10-22 | Pfizer Inc. | Substituted tetralins, chromans and related compounds in the treatment of asthma, arthritis and related diseases |
Cited By (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998011085A1 (en) * | 1996-09-16 | 1998-03-19 | Pfizer Inc. | Processes and intermediates for preparing substituted chromanol derivatives |
CN1108298C (en) * | 1996-09-16 | 2003-05-14 | 辉瑞大药厂 | Processes and intermediates for preparing substituted chromanol derivatives |
WO2001034563A1 (en) * | 1999-10-27 | 2001-05-17 | Nobex Corporation | Resolution of intermediates in the synthesis of substantially pure bicalutamide |
US6593492B1 (en) | 1999-10-27 | 2003-07-15 | Nobex Corporation | Resolution of intermediates in the synthesis of substantially pure bicalutamide |
US6482848B2 (en) | 2000-05-24 | 2002-11-19 | Sugen Incorporated | Prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives |
US6479692B1 (en) | 2001-05-02 | 2002-11-12 | Nobex Corporation | Methods of synthesizing acylanilides including bicalutamide and derivatives thereof |
US6812362B2 (en) | 2001-05-02 | 2004-11-02 | Nobex Corporation | Methods of synthesizing acylanilides including bicalutamide and derivatives thereof |
US8957109B2 (en) | 2004-09-21 | 2015-02-17 | Mei Pharma, Inc. | Chroman derivatives, medicaments and use in therapy |
US8080675B2 (en) | 2004-09-21 | 2011-12-20 | Marshall Edwards, Inc. | Chroman derivatives, medicaments and use in therapy |
US8084628B2 (en) | 2004-09-21 | 2011-12-27 | Marshall Edwards, Inc. | Substituted chroman derivatives, medicaments and use in therapy |
US8461361B2 (en) | 2004-09-21 | 2013-06-11 | Marshall Edwards, Inc. | Chroman derivatives, medicaments and use in therapy |
US8697891B2 (en) | 2004-09-21 | 2014-04-15 | Marshall Edwards, Inc. | Substituted chroman derivatives, medicaments and use in therapy |
US7601855B2 (en) | 2004-09-21 | 2009-10-13 | Novogen Research Pty Ltd | Substituted chroman derivatives, medicaments and use in therapy |
US9138478B2 (en) | 2004-09-21 | 2015-09-22 | Mei Pharma, Inc. | Substituted chroman derivatives, medicaments and use in therapy |
US9198895B2 (en) | 2004-09-21 | 2015-12-01 | Mei Pharma, Inc. | Chroman derivatives, medicaments and use in therapy |
US9381186B2 (en) | 2004-09-21 | 2016-07-05 | Mei Pharma, Inc. | Substituted chroman derivatives, medicaments and use in therapy |
US9663484B2 (en) | 2010-11-01 | 2017-05-30 | Mei Pharma, Inc. | Isoflavonoid compounds and methods for the treatment of cancer |
US9708283B2 (en) | 2010-11-01 | 2017-07-18 | Mei Pharma, Inc. | Isoflavonoid compositions and methods for the treatment of cancer |
US9981936B2 (en) | 2010-11-01 | 2018-05-29 | Mei Pharma, Inc. | Isoflavonoid compositions and methods for the treatment of cancer |
US10105346B2 (en) | 2010-11-01 | 2018-10-23 | Mei Pharma, Inc. | Isoflavonoid compounds and methods for the treatment of cancer |
US10369132B2 (en) | 2010-11-01 | 2019-08-06 | Mei Pharma, Inc. | Isoflavonoid compositions and methods for the treatment of cancer |
US10973799B2 (en) | 2010-11-01 | 2021-04-13 | Mei Pharma, Inc. | Isoflavonoid compositions and methods for the treatment of cancer |
US11583514B2 (en) | 2010-11-01 | 2023-02-21 | Mei Pharma, Inc. | Isoflavonoid compounds and methods for the treatment of cancer |
US11723893B2 (en) | 2010-11-01 | 2023-08-15 | Mei Pharma, Inc. | Isoflavonoid compositions and methods for the treatment of cancer |
US10980774B2 (en) | 2015-02-02 | 2021-04-20 | Mei Pharma, Inc. | Combination therapies |
Also Published As
Publication number | Publication date |
---|---|
CZ100895A3 (en) | 1995-10-18 |
AU4650493A (en) | 1994-05-09 |
EP0665839A1 (en) | 1995-08-09 |
NO951507D0 (en) | 1995-04-20 |
CA2146005A1 (en) | 1994-04-28 |
MX9306526A (en) | 1994-04-29 |
NO951507L (en) | 1995-04-20 |
PL308473A1 (en) | 1995-08-07 |
JPH07507811A (en) | 1995-08-31 |
HUT65128A (en) | 1994-04-28 |
MY131378A (en) | 2007-08-30 |
KR950704291A (en) | 1995-11-17 |
CN1090577A (en) | 1994-08-10 |
IL107293A0 (en) | 1994-01-25 |
FI934624A (en) | 1994-04-22 |
FI934624A0 (en) | 1993-10-20 |
ZA937737B (en) | 1995-04-19 |
HU9302973D0 (en) | 1993-12-28 |
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