EP0665839A1 - $i(ENANTIOMERIC CIS)-3-(4,6-DIHYDROXYCHROMAN-3-YLMETHYL)BENZOIC ACIDS - Google Patents
$i(ENANTIOMERIC CIS)-3-(4,6-DIHYDROXYCHROMAN-3-YLMETHYL)BENZOIC ACIDSInfo
- Publication number
- EP0665839A1 EP0665839A1 EP93916752A EP93916752A EP0665839A1 EP 0665839 A1 EP0665839 A1 EP 0665839A1 EP 93916752 A EP93916752 A EP 93916752A EP 93916752 A EP93916752 A EP 93916752A EP 0665839 A1 EP0665839 A1 EP 0665839A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- dihydroxychroman
- compound
- salt
- benzoic acid
- ylmethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96433692A | 1992-10-21 | 1992-10-21 | |
| US964336 | 1992-10-21 | ||
| PCT/US1993/006061 WO1994008986A1 (en) | 1992-10-21 | 1993-06-30 | Enantiomeric cis-3-(4,6-dihydroxychroman-3-yl-methyl)benzoic acids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0665839A1 true EP0665839A1 (en) | 1995-08-09 |
Family
ID=25508434
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP93916752A Withdrawn EP0665839A1 (en) | 1992-10-21 | 1993-06-30 | $i(ENANTIOMERIC CIS)-3-(4,6-DIHYDROXYCHROMAN-3-YLMETHYL)BENZOIC ACIDS |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP0665839A1 (hu) |
| JP (1) | JPH07507811A (hu) |
| KR (1) | KR950704291A (hu) |
| CN (1) | CN1090577A (hu) |
| AU (1) | AU4650493A (hu) |
| CA (1) | CA2146005A1 (hu) |
| CZ (1) | CZ100895A3 (hu) |
| FI (1) | FI934624A (hu) |
| HU (1) | HUT65128A (hu) |
| IL (1) | IL107293A0 (hu) |
| MX (1) | MX9306526A (hu) |
| MY (1) | MY131378A (hu) |
| NO (1) | NO951507L (hu) |
| PL (1) | PL308473A1 (hu) |
| WO (1) | WO1994008986A1 (hu) |
| ZA (1) | ZA937737B (hu) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU713701B2 (en) * | 1996-09-16 | 1999-12-09 | Pfizer Inc. | Processes and intermediates for preparing substituted chromanol derivatives |
| MXPA02004225A (es) * | 1999-10-27 | 2002-10-17 | Nobex Corp | Resolucion de intermediarios en la sintesis de bicalutamida sustancialmente pura. |
| TWI270545B (en) | 2000-05-24 | 2007-01-11 | Sugen Inc | Mannich base 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 |
| US8080675B2 (en) | 2004-09-21 | 2011-12-20 | Marshall Edwards, Inc. | Chroman derivatives, medicaments and use in therapy |
| ATE532777T1 (de) | 2004-09-21 | 2011-11-15 | Marshall Edwards Inc | Substituierte chromanderivate, medikamente und anwendungen in der therapie |
| CA2816322A1 (en) | 2010-11-01 | 2012-05-10 | Marshall Edwards, Inc. | Isoflavonoid compositions and methods for the treatment of cancer |
| AU2016215515B2 (en) | 2015-02-02 | 2020-04-30 | Mei Pharma, Inc. | Combination therapies |
Family Cites Families (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 KR KR1019950701524A patent/KR950704291A/ko not_active Application Discontinuation
- 1993-06-30 AU AU46504/93A patent/AU4650493A/en not_active Abandoned
- 1993-06-30 WO PCT/US1993/006061 patent/WO1994008986A1/en not_active Application Discontinuation
- 1993-06-30 CA CA002146005A patent/CA2146005A1/en not_active Abandoned
- 1993-06-30 JP JP6509963A patent/JPH07507811A/ja active Pending
- 1993-06-30 EP EP93916752A patent/EP0665839A1/en not_active Withdrawn
- 1993-06-30 PL PL93308473A patent/PL308473A1/xx unknown
- 1993-06-30 CZ CZ951008A patent/CZ100895A3/cs unknown
- 1993-10-14 IL IL107293A patent/IL107293A0/xx unknown
- 1993-10-19 ZA ZA937737A patent/ZA937737B/xx unknown
- 1993-10-20 FI FI934624A patent/FI934624A/fi not_active Application Discontinuation
- 1993-10-20 MX MX9306526A patent/MX9306526A/es unknown
- 1993-10-20 MY MYPI93002174A patent/MY131378A/en unknown
- 1993-10-20 CN CN93119050A patent/CN1090577A/zh active Pending
- 1993-10-20 HU HU9302973A patent/HUT65128A/hu unknown
-
1995
- 1995-04-20 NO NO951507A patent/NO951507L/no unknown
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9408986A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| FI934624A0 (fi) | 1993-10-20 |
| NO951507D0 (no) | 1995-04-20 |
| MX9306526A (es) | 1994-04-29 |
| PL308473A1 (en) | 1995-08-07 |
| KR950704291A (ko) | 1995-11-17 |
| MY131378A (en) | 2007-08-30 |
| FI934624A (fi) | 1994-04-22 |
| CZ100895A3 (en) | 1995-10-18 |
| IL107293A0 (en) | 1994-01-25 |
| AU4650493A (en) | 1994-05-09 |
| JPH07507811A (ja) | 1995-08-31 |
| HUT65128A (en) | 1994-04-28 |
| CN1090577A (zh) | 1994-08-10 |
| WO1994008986A1 (en) | 1994-04-28 |
| NO951507L (no) | 1995-04-20 |
| ZA937737B (en) | 1995-04-19 |
| HU9302973D0 (en) | 1993-12-28 |
| CA2146005A1 (en) | 1994-04-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 19950411 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU NL PT SE |
|
| 17Q | First examination report despatched |
Effective date: 19960307 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 19960718 |