Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-05-08
2000-11-07
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548231, 548232, A61K 3142, A61P 2524, A61P 2518, C07D26316, C07D41304
Patent
active
061437727
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to compounds derived from 3-(benzofuran-5-yl)oxazolidin-2-one, a process for their preparation and their application in therapeutics.
The compounds of the invention correspond to the general formula (I) ##STR2## in which: R.sub.1 represents a phenyl group, a phenylmethyl group, an alkyl group comprising 3 to 6 carbon atoms or a fluoroalkyl group comprising 1 to 6 carbon atoms, and R.sub.2 represents a hydrogen atom or a methyl group.
In the context of the present invention: least one of the carbon atoms is substituted by one or more fluorine atoms. fluorine atoms substituted onto the carbon atom at the end of the alkyl chain.
The compounds of formula (I) have an asymmetric carbon atom. They can thus exist in the form of enantiomers. The invention comprises the pure enantiomers as well as their mixtures, including their racemic mixtures.
Preferred compounds of formula (I) are those for which or a 3,3,3-trifluoropropyl group and/or
The compounds of formula (I) can be prepared according to the process represented in the annexed scheme 1, starting from a compound of formula (II) ##STR3## in which R.sub.1 is defined as in the formula (I).
This process consists in reducing the nitro group of the compound of formula (II), in reacting the compound of formula (III) ##STR4## with ethyl chloroformate and sodium bicarbonate to obtain the compound of formula (IV) ##STR5## where Et is an ethyl group and R.sub.1 is as defined above. The compound of formula (IV) can then be reacted with 4-methoxymethyl-1,3-dioxolan-2-one to prepare the compounds of formula (I) where R.sub.2 is a methyl group. Then, said compound of formula (I) where R.sub.2 is a methyl group can be treated with boron tribromide to obtain the compounds of formula (I) where R.sub.2 is a hydrogen atom.
The compounds of formula (II) can be prepared according to the process represented in scheme 2 below: ##STR6## which consists in treating (2-hydroxy-5-nitrophenyl)-methyltriphenylphosphonium bromide (compound described in Chem. Ber. 1986, 119, 2169) with an acid chloride of formula R.sub.1 COCl in which R.sub.1 is defined as in the formula (I).
The 5 (R) and 5 (S) isomers of the compounds of formula (I) are prepared by reaction of a compound of formula (IV) with the 4 (S) and 4 (R) isomers of 4-methoxymethyl-1,3-dioxolan-2-one respectively.
4 (S)-Methoxymethyl-1,3-dioxolan-2-one is a known compound whose preparation is described in U.S. Pat. No. 5,264,443.
4 (R)-Methoxymethyl-1,3-dioxolan-2-one is prepared according to the same method, starting from (R)-2,2-dimethyl-1,3-dioxolan-4-methanol.
The following examples illustrate the present invention.
EXAMPLE 1
3-[2-(3,3,3-trifluoropropyl)benzofuran-5-yl]-5
(R)-methoxymethyloxazolidin-2-one
A suspension of 4.0 g (8.1 mmol) of (2-hydroxy-5-nitrophenyl) methyltriphenylphosphonium bromide in 50 ml of toluene is heated to reflux, then 5.1 ml (36 mmol) of triethylamine and 1.9 g (12 mmol) of 4,4,4-trifluorobutyryl chloride are added. The mixture is stirred for 2 hours, then it is filtered and the filtrate is concentrated under reduced pressure. By chromatography of the residue on a silica column using a 0-30% mixture of dichloromethane in cyclohexane, 1.1 g of product are obtained. Melting point: 70-71.degree. C.
A mixture of 2.4 g (9.2 mmol) of 2-(3,3,3-trifluoropropyl)-5-nitrobenzofuran, 0.65 g (17 mmol) of sodium borohydride, 45 mg of Adogen.RTM. 464 (methyl trialkylammonium chloride) and 0.38 g of 5% palladium on carbon containing 50% of water in 95 ml of dichloromethane and 48 ml of water is stirred for 5 hours, then it is filtered on silica and the silica is rinsed with ethanol. The filtrate is then concentrated under reduced pressure and coevaporated with toluene. By chromatography of the residue on a silica column using a 0-30% mixture of ethyl acetate in cyclohexane, 2.0 g of product are obtained. Melting point: 74.degree. C.
A solution of 2.0 g (8.7 mmol) of 5-amino-2-(3,3,3-trifluoropropyl) benzofuran in 30 ml of a 9/1 mixture of tetrahydrofuran and water is reacted for 30
REFERENCES:
patent: 3654298 (1972-04-01), Douzon et al.
patent: 4250318 (1981-02-01), Dostert et al.
patent: 4259338 (1981-03-01), Paioni et al.
patent: 4461773 (1984-07-01), Gregory
patent: 4476136 (1984-10-01), Dostert et al.
patent: 4517197 (1985-05-01), Ancher et al.
patent: 5036090 (1991-07-01), Jarreau et al.
patent: 5036091 (1991-07-01), Jarreau et al.
patent: 5171747 (1992-12-01), Jarreau et al.
patent: 5196543 (1993-03-01), Jarreau et al.
patent: 5235063 (1993-08-01), Jarreau et al.
patent: 5684023 (1997-11-01), Riedl et al.
Berthon Danielle
Burnier Philippe
Jegham Samir
Puech Frederic
Coleman Brenda
Shah Mukund J.
Synthelabo
LandOfFree
Compounds derived from 3-(benzofuran-5-yl)oxazolidin-2-one, prep does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compounds derived from 3-(benzofuran-5-yl)oxazolidin-2-one, prep, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compounds derived from 3-(benzofuran-5-yl)oxazolidin-2-one, prep will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1641536