USRE39755E1 - 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a process for the preparation thereof and the use thereof - Google Patents
3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a process for the preparation thereof and the use thereof Download PDFInfo
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- USRE39755E1 USRE39755E1 US11/050,627 US5062705A USRE39755E US RE39755 E1 USRE39755 E1 US RE39755E1 US 5062705 A US5062705 A US 5062705A US RE39755 E USRE39755 E US RE39755E
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- United States
- Prior art keywords
- benzofuran
- nitro
- salt
- pentanoic acid
- formula
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- Expired - Lifetime
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- 238000000034 method Methods 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- RJMPDGNCDFVLHH-UHFFFAOYSA-N 3-(1-hydroxypentylidene)-5-nitro-1-benzofuran-2-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=C(O)CCCC)C(=O)OC2=C1 RJMPDGNCDFVLHH-UHFFFAOYSA-N 0.000 title abstract description 7
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 7
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 239000011541 reaction mixture Substances 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- OFONKIRKKMJQLZ-UHFFFAOYSA-N 5-nitro-3h-1-benzofuran-2-one Chemical compound [O-][N+](=O)C1=CC=C2OC(=O)CC2=C1 OFONKIRKKMJQLZ-UHFFFAOYSA-N 0.000 claims description 7
- DUCKXCGALKOSJF-UHFFFAOYSA-N pentanoyl pentanoate Chemical compound CCCCC(=O)OC(=O)CCCC DUCKXCGALKOSJF-UHFFFAOYSA-N 0.000 claims description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- MHHWPBSIZBYLME-UHFFFAOYSA-N 5-nitro-3-pentanoyl-3h-1-benzofuran-2-one Chemical compound C1=C([N+]([O-])=O)C=C2C(C(=O)CCCC)C(=O)OC2=C1 MHHWPBSIZBYLME-UHFFFAOYSA-N 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 abstract description 6
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- XGAJABPTUOLUAE-UHFFFAOYSA-N 2-butyl-5-nitro-1-benzofuran Chemical compound [O-][N+](=O)C1=CC=C2OC(CCCC)=CC2=C1 XGAJABPTUOLUAE-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- JWPKVGMPWIXZKC-VHPXAQPISA-N CCCC/C(O)=C1\C(=O)OC2=C1C=C([N+](=O)[O-])C=C2.CCCCC(=O)C1C(=O)OC2=C1C=C([N+](=O)[O-])C=C2 Chemical compound CCCC/C(O)=C1\C(=O)OC2=C1C=C([N+](=O)[O-])C=C2.CCCCC(=O)C1C(=O)OC2=C1C=C([N+](=O)[O-])C=C2 JWPKVGMPWIXZKC-VHPXAQPISA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- ZQTNQVWKHCQYLQ-UHFFFAOYSA-N dronedarone Chemical compound C1=CC(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(CCCC)OC2=CC=C(NS(C)(=O)=O)C=C12 ZQTNQVWKHCQYLQ-UHFFFAOYSA-N 0.000 description 2
- 229960002084 dronedarone Drugs 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- RJMPDGNCDFVLHH-ZRDIBKRKSA-N CCCC/C(O)=C1\C(=O)OC2=C1C=C([N+](=O)[O-])C=C2 Chemical compound CCCC/C(O)=C1\C(=O)OC2=C1C=C([N+](=O)[O-])C=C2 RJMPDGNCDFVLHH-ZRDIBKRKSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000000643 oven drying Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229940072033 potash Drugs 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D307/83—Oxygen atoms
Definitions
- the present invention relates to 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one and to its ketonic tautomer form 3-(1-oxo-pentyl)-5-nitro-3H-benzofuran-2-one.
- 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one is a new compound which may be used as a synthesis intermediate. In particular, it may be converted to 2-butyl-5-nitrobenzofuran by hydrolysis, decarboxylation and cyclisation, by simple heating in an acid medium.
- 2-butyl-5-nitrobenzofuran may act as an intermediate in the synthesis of an antiarrythmic, dronedarone.
- the present invention provides, therefore, 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one corresponding to formula (I) and its ketonic tautomer form, 3-(1-oxo-pentyl)-5-nitro-3H-benzofuran-2-one corresponding to formula (II)
- the present invention also provides a process for the preparation of the compound corresponding to formula (I) and its ketonic tautomer form (II).
- the present invention provides the use of the compound corresponding to formula (I) or its ketonic tautomer form (II) as a synthesis intermediate, particularly for the preparation of active pharmaceutical principles.
- the present invention provides the compound corresponding to formula (I) and the preparation thereof.
- This preparation is characterised in that 5-nitro-3H-benzofuran-2-one is reacted, at a temperature above 30° C., with pentanoic anhydride and a salt of pentanoic acid, optionally in the presence of pentanoic acid, then the resulting reaction mixture is acidified, and then the expected product is isolated.
- This improvement to the process relates to the acidification of the reaction mixture at the end of the reaction which allows better isolation of the expected product.
- a second improvement relates to the reduction in the amount of acid anhydride required for the reaction.
- one mole of 5-nitro-3H-benzofuran-2-one is reacted with two moles of pentanoic anhydride and one mole of a salt of pentanoic acid, then the resulting reaction mixture is acidified, then the expected product is isolated.
- the salt of pentanoic acid may be a salt of sodium, potassium or of tertiary amine.
- This salt may be prepared extemporaneously, preferably in situ, from pentanoic acid and a base.
- the base may be sodium carbonate.
- the resulting reaction mixture is brought into contact with an acid.
- This acid will be preferably dilute sulfuric acid; indeed, it permits better recovery of the expected final product.
- the crude product obtained may be recrystallised in an acid.
- This acid will be advantageously acetic acid.
- the present invention also provides the use of the product corresponding to formula (I) or its tautomeric form (II) for the production of synthesis intermediates.
- it provides the production of 2-butyl-5-nitro-benzofuran-2-one 2 - butyl - 5 - nitro - benzofuran which may act as an intermediate in the synthesis of an antiarrhythmic agent, dronedarone.
- the temperature of the mixture rises to about 40° C.
- the suspension is then cooled to 20° C. and the precipitate is filtered. It is washed with 250 ml of deionised water then with 250 ml of heptane.
- the mixture is brought to reflux, with stirring, over a period of 8 hours, the internal temperature being in the vicinity of 116° C.
- the solution is cooled to ambient temperature and 50 g of water are added, then the solution is extracted twice under hot conditions with 140 g of heptane.
- the combined organic phases are treated with 250 g of water and the pH is adjusted to 8 by adding a 30% potash solution (about 20 ml), then the aqueous phase is drawn off.
- the separated organic phase is then dried by azeotropic distillation of water then the solvent is removed by distillation and the resulting oil is heated under reduced pressure in order to remove the traces of solvent.
- the 2-butyl-5-nitrobenzofuran obtained has a purity (high pressure liquid chromatography by external standardisation with respect to a reference standard) greater than 98% and a residual amount of heptane, by vapour phase chromatography, of less than 1.5%.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
A product corresponding to formula (I) or its ketonic tautomer form (II)
which is 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one, a process for the preparation and use of the product corresponding to formula (I) or its tautomeric form (II), a process for the preparation and use, particularly for the production of synthesis intermediates.
which is 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one, a process for the preparation and use of the product corresponding to formula (I) or its tautomeric form (II), a process for the preparation and use, particularly for the production of synthesis intermediates.
Description
The present invention relates to 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one and to its ketonic tautomer form 3-(1-oxo-pentyl)-5-nitro-3H-benzofuran-2-one.
3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one is a new compound which may be used as a synthesis intermediate. In particular, it may be converted to 2-butyl-5-nitrobenzofuran by hydrolysis, decarboxylation and cyclisation, by simple heating in an acid medium.
2-butyl-5-nitrobenzofuran may act as an intermediate in the synthesis of an antiarrythmic, dronedarone.
The present invention provides, therefore, 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one corresponding to formula (I)
and its ketonic tautomer form, 3-(1-oxo-pentyl)-5-nitro-3H-benzofuran-2-one corresponding to formula (II) 
and its ketonic tautomer form, 3-(1-oxo-pentyl)-5-nitro-3H-benzofuran-2-one corresponding to formula (II)
The present invention also provides a process for the preparation of the compound corresponding to formula (I) and its ketonic tautomer form (II).
Finally, the present invention provides the use of the compound corresponding to formula (I) or its ketonic tautomer form (II) as a synthesis intermediate, particularly for the preparation of active pharmaceutical principles.
In particular, the present invention provides the compound corresponding to formula (I) and the preparation thereof.
This preparation is characterised in that 5-nitro-3H-benzofuran-2-one is reacted, at a temperature above 30° C., with pentanoic anhydride and a salt of pentanoic acid, optionally in the presence of pentanoic acid, then the resulting reaction mixture is acidified, and then the expected product is isolated.
This method of operating constitutes an improvement to the process described by J. N. Chatterjea, J. Indian Chem. Soc. Vol. 33 no. 3, 1956, p. 175-182 and J. Indian Chem. Soc. Vol. 34, no.4, 1957, p. 299-305.
This improvement to the process relates to the acidification of the reaction mixture at the end of the reaction which allows better isolation of the expected product. A second improvement relates to the reduction in the amount of acid anhydride required for the reaction.
Under preferential conditions for carrying out the process according to the invention, 1 mole of 5-nitro-3H-benzofuran-2-one is reacted with 1 to 5 moles of pentanoic anhydride, 0.1 to 2 moles of a salt of pentanoic acid, and 0 to 1.5 moles of pentanoic acid, then the resulting reaction mixture is acidified, and then the expected product is isolated, if desired.
Under other preferential conditions for carrying out the process according to the invention, one mole of 5-nitro-3H-benzofuran-2-one is reacted with two moles of pentanoic anhydride and one mole of a salt of pentanoic acid, then the resulting reaction mixture is acidified, then the expected product is isolated.
In the implementation of the process according to the invention, the salt of pentanoic acid may be a salt of sodium, potassium or of tertiary amine. This salt may be prepared extemporaneously, preferably in situ, from pentanoic acid and a base. The base may be sodium carbonate.
In the implementation of the process according to the invention, the resulting reaction mixture is brought into contact with an acid. This acid will be preferably dilute sulfuric acid; indeed, it permits better recovery of the expected final product.
Still under preferential conditions for carrying out the process, the crude product obtained may be recrystallised in an acid. This acid will be advantageously acetic acid.
The present invention also provides the use of the product corresponding to formula (I) or its tautomeric form (II) for the production of synthesis intermediates. In particular, it provides the production of 2-butyl-5-nitro-benzofuran-2-one 2-butyl- 5 -nitro-benzofuran which may act as an intermediate in the synthesis of an antiarrhythmic agent, dronedarone.
The examples below will permit a better understanding of the invention.
The following are charged to a three-necked flask:
-
- 478.7 g (2.57 moles) of pentanoic anhydride
- 131.3 g (1.285 moles) of pentanoic acid
- 81.6 g (0.771 mole) of sodium carbonate
- 230 g (1.285 moles) of 5-nitro-3H-benzofuran-2-one and the mixture is raised to a temperature of 80° C. for a period of 6 hours, with stirring.
The mixture is cooled to 20° C. and the following are added gradually within 15 minutes:
-
- 377.8 g (0.771 mole) of sulfuric acid diluted to 20%.
The temperature of the mixture rises to about 40° C.
The suspension is then cooled to 20° C. and the precipitate is filtered. It is washed with 250 ml of deionised water then with 250 ml of heptane.
After oven drying under reduced pressure at 60° C., a crude product with a purity of 95% is obtained.
Pure 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one is obtained by recrystallisation in acetic acid.
The analysis of the product is as follows:
| Melting point: | 164° C. (DSC) |
| Elemental analysis (theoretical): | C 59.1% (59.3%), H 5.0% (4.9%), N |
| 5.4% (5.3%) | |
| NMR (H): | 200 MHz |
| Solvent: | DMSO |
| δ = 0.90 ppm | Triplet | J=7.1Hz | 3H |
| δ = 1.37 ppm | Multiplet | 2H | |
| δ = 1.60 ppm | Multiplet | 2H | |
| δ = 2.94 ppm | Triplet | J=7.9Hz | 2H |
| δ = 7.30 ppm | Doublet | JH7-H6=8.9Hz | 1H |
| δ = 8.05 ppm | Quadruplet | JH6-H7=8.9Hz; JH6-H4=2.3Hz | 1H |
| δ = 8.38 ppm | Doublet | JH4-H6=2.3Hz | 1H |
The following are charged to a three-necked flask:
-
- 96 g (1.6 moles) of 100% acetic acid
- 49 g (0.2 mole) of 40% sulfuric acid
- 26.3 g (0.1 mole) of 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one.
The mixture is brought to reflux, with stirring, over a period of 8 hours, the internal temperature being in the vicinity of 116° C.
An orange-coloured solution is gradually obtained with the liberation of gas.
The solution is cooled to ambient temperature and 50 g of water are added, then the solution is extracted twice under hot conditions with 140 g of heptane.
The combined organic phases are treated with 250 g of water and the pH is adjusted to 8 by adding a 30% potash solution (about 20 ml), then the aqueous phase is drawn off.
The separated organic phase is then dried by azeotropic distillation of water then the solvent is removed by distillation and the resulting oil is heated under reduced pressure in order to remove the traces of solvent.
A slightly yellow oil which crystallises at ambient temperature is thus obtained.
The 2-butyl-5-nitrobenzofuran obtained has a purity (high pressure liquid chromatography by external standardisation with respect to a reference standard) greater than 98% and a residual amount of heptane, by vapour phase chromatography, of less than 1.5%.
The NMR (H) spectrum 200 MHz (solvent: DMSO) is as follows:
| δ = 0.90 ppm | Triplet | J=7.2Hz | 3H | ||
| δ = 1.35 ppm | Multiplet | 2H | |||
| δ = 1.66 ppm | Multiplet | 2H | |||
| δ = 2.80 ppm | Triplet | J=7.4Hz | 2H | ||
| δ = 6.80 ppm | Singlet | 1H | |||
| δ = 7.70 ppm | Doublet | JH7H6=9Hz | 1H | ||
| δ = 8.11 ppm | Doublet of | JH6H7=9Hz; JH6H42.3Hz | 1H | ||
| doublet | |||||
| δ = 8.47 ppm | Doublet | JH4H62.3Hz | 1H | ||
Claims (13)
1. A compound having the formula (I) or its ketonic tautomer form (II)
2. A compound having the formula I according to claim 1 , which is 3(1-hydroxy-pentylidene)-5nitro-3H-benzofuran-2-one.
3. A compound to formula II according to claim 2 which is 3-(1-oxopentyl)-5-nitro-3H-benzofuran-2-one.
4. A process for the preparation of the compound having the formula (I) or (II),
in which 5-nitro-3H-benzofuran-2-one is reacted, at a temperature above 30° C., with pentanoic anhydride and a salt of pentanoic acid, optionally in the presence of pentanoic acid, then the resulting reaction mixture is acidified, and then the above compound is isolated.
5. A process according to claim 4 , in which 1 mole of 5-nitro-3H-benzofuran-2-one is reacted with 1 to 5 moles of pentanoic anhydride, 0.1 to 2 moles of a salt of pentanoic acid and 0 to 1.5 moles of pentanoic acid, then the resulting reaction mixture is acidified and then the above compound is isolated.
6. A process according to claim 4 , in which 1 mole of 5-nitro-3H-benzofuran-2-one is reacted with 2 moles of pentanoic anhydride and 1 mole of a salt of pentanoic acid, then the resulting reaction mixture is acidified, and then the above compound is isolated.
7. A process according to claim 4 , in which the salt of pentanoic acid is the salt of sodium, potassium or a salt of tertiary amine.
8. A prowess process according to claim 4 , in which the salt of pentanoic acid is produced extemporaneously from pentanoic acid and a base.
9. A process according to claim 4 , in which the salt of pentanoic acid is produced in situ from pentanoic acid and sodium carbonate.
10. A process according to claim 4 , in which the reaction mixture is acidified with sulfuric acid.
11. A process according to claim 4 , in which the above formula (I) or its tautomeric form (II) is purified by recrystallisation in acetic acid.
12. Synthesis intermediate produced using the compound of formula (I) or of its tautomeric form (II) as claimed in claim 1 .
13. 2-butyl-5-nitro-benzofuran-2-one produced using the compound of formula (I) or of its tautomeric form (II) as claimed in claim 1 .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/050,627 USRE39755E1 (en) | 2000-01-17 | 2005-02-03 | 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a process for the preparation thereof and the use thereof |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0000523A FR2803846B1 (en) | 2000-01-17 | 2000-01-17 | 3- (1-HYDROXY-PENTYLIDENE) -5-NITRO-3H-BENZOFURAN-2-ONE, ITS PREPARATION PROCESS AND ITS USE |
| US09/761,452 US6515147B2 (en) | 2000-01-17 | 2001-01-17 | 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a process for the preparation thereof and the use thereof |
| US11/050,627 USRE39755E1 (en) | 2000-01-17 | 2005-02-03 | 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a process for the preparation thereof and the use thereof |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/761,452 Reissue US6515147B2 (en) | 2000-01-17 | 2001-01-17 | 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a process for the preparation thereof and the use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| USRE39755E1 true USRE39755E1 (en) | 2007-07-31 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/761,452 Ceased US6515147B2 (en) | 2000-01-17 | 2001-01-17 | 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a process for the preparation thereof and the use thereof |
| US11/050,627 Expired - Lifetime USRE39755E1 (en) | 2000-01-17 | 2005-02-03 | 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a process for the preparation thereof and the use thereof |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/761,452 Ceased US6515147B2 (en) | 2000-01-17 | 2001-01-17 | 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a process for the preparation thereof and the use thereof |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US6515147B2 (en) |
| EP (1) | EP1116719B1 (en) |
| JP (1) | JP4408578B2 (en) |
| KR (1) | KR100788529B1 (en) |
| CN (1) | CN1204133C (en) |
| AT (1) | ATE292630T1 (en) |
| DE (1) | DE60109829T2 (en) |
| DK (1) | DK1116719T3 (en) |
| ES (1) | ES2238408T3 (en) |
| FR (1) | FR2803846B1 (en) |
| HU (1) | HUP0100146A3 (en) |
| NO (1) | NO327039B1 (en) |
| TW (1) | TW564246B (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10237819A1 (en) | 2002-08-19 | 2004-03-04 | Bayer Ag | 5-Nitrobenzofurane |
| FR2864536B1 (en) * | 2003-12-24 | 2006-03-17 | Clariant France Sa | PROCESS FOR THE PREPARATION OF N-ALKYL-2 (HYDROXY-4-BENZOYL) -3 BENZOFURANES AND INTERMEDIATES FOR CARRYING OUT SAID METHOD |
| GB0719180D0 (en) * | 2007-10-02 | 2007-11-14 | Cambrex Karlskoga Ab | New process |
| EP3195862A1 (en) * | 2008-04-17 | 2017-07-26 | Sanofi | Use of dronedarone for the preparation of a medicament for use in the prevention of cardiovascular hospitalization or in the prevention of atrial fibrillation |
| FR2930149B1 (en) * | 2008-04-17 | 2011-02-18 | Sanofi Aventis | ASSOCIATION OF DRONEDARONE WITH AT LEAST ONE DIURETIC, ITS THERAPEUTIC APPLICATION |
| EP2116239A1 (en) * | 2008-04-29 | 2009-11-11 | Sanofi-Aventis | Method for managing the risks associated with an increase in serum creatinine during dronedarone treatment |
| EP2246341A1 (en) | 2009-01-23 | 2010-11-03 | Lonza Ltd. | Process for preparing 2-Alkyl-3-aroyl-5-nitro-benzofurans |
| CN102276561A (en) * | 2010-06-09 | 2011-12-14 | 江苏恒瑞医药股份有限公司 | Preparation method of Dronedarone and its salt |
| US8602215B2 (en) | 2010-06-30 | 2013-12-10 | Sanofi | Methods for reducing the risk of an adverse dronedarone/beta-blockers interaction in a patient suffering from atrial fibrillation |
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| US5223510A (en) * | 1990-08-06 | 1993-06-29 | Sanofi | Alkylaminoalkyl derivatives of benzofuran, benzothiophene, indole and indolizine, process for their preparation and compositions containing them |
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| WO1996005190A1 (en) | 1994-08-11 | 1996-02-22 | Karo Bio Ab | 3-benzoyl benzofuran derivatives as thyroid hormone antagonists |
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2000
- 2000-01-17 FR FR0000523A patent/FR2803846B1/en not_active Expired - Fee Related
-
2001
- 2001-01-10 TW TW090100495A patent/TW564246B/en not_active IP Right Cessation
- 2001-01-15 EP EP01810033A patent/EP1116719B1/en not_active Expired - Lifetime
- 2001-01-15 DE DE60109829T patent/DE60109829T2/en not_active Expired - Lifetime
- 2001-01-15 AT AT01810033T patent/ATE292630T1/en active
- 2001-01-15 DK DK01810033T patent/DK1116719T3/en active
- 2001-01-15 ES ES01810033T patent/ES2238408T3/en not_active Expired - Lifetime
- 2001-01-15 HU HU0100146A patent/HUP0100146A3/en unknown
- 2001-01-16 JP JP2001007465A patent/JP4408578B2/en not_active Expired - Fee Related
- 2001-01-16 NO NO20010265A patent/NO327039B1/en not_active IP Right Cessation
- 2001-01-16 KR KR1020010002333A patent/KR100788529B1/en not_active Expired - Fee Related
- 2001-01-17 US US09/761,452 patent/US6515147B2/en not_active Ceased
- 2001-01-17 CN CNB01101296XA patent/CN1204133C/en not_active Expired - Fee Related
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2005
- 2005-02-03 US US11/050,627 patent/USRE39755E1/en not_active Expired - Lifetime
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| US3248401A (en) | 1966-04-26 | Diethylaminoe hoxybenzoyl benzofurans | ||
| US4252817A (en) | 1975-03-12 | 1981-02-24 | Sandoz Ltd. | Substituted-2,3-dihydrobenzofuran-2-ones |
| US5444056A (en) * | 1989-02-07 | 1995-08-22 | Sanofi | Aminoalkoxyphenyl derivatives, process for their preparation and compositions containing them |
| US5223510A (en) * | 1990-08-06 | 1993-06-29 | Sanofi | Alkylaminoalkyl derivatives of benzofuran, benzothiophene, indole and indolizine, process for their preparation and compositions containing them |
| WO1996005190A1 (en) | 1994-08-11 | 1996-02-22 | Karo Bio Ab | 3-benzoyl benzofuran derivatives as thyroid hormone antagonists |
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Also Published As
| Publication number | Publication date |
|---|---|
| ES2238408T3 (en) | 2005-09-01 |
| FR2803846A1 (en) | 2001-07-20 |
| KR20010076278A (en) | 2001-08-11 |
| DE60109829D1 (en) | 2005-05-12 |
| JP2001233870A (en) | 2001-08-28 |
| HUP0100146A3 (en) | 2003-07-28 |
| EP1116719B1 (en) | 2005-04-06 |
| US20010012900A1 (en) | 2001-08-09 |
| HUP0100146A2 (en) | 2002-01-28 |
| NO20010265L (en) | 2001-07-18 |
| FR2803846B1 (en) | 2002-04-05 |
| EP1116719A2 (en) | 2001-07-18 |
| TW564246B (en) | 2003-12-01 |
| DK1116719T3 (en) | 2005-07-18 |
| ATE292630T1 (en) | 2005-04-15 |
| DE60109829T2 (en) | 2006-01-19 |
| HU0100146D0 (en) | 2001-03-28 |
| NO20010265D0 (en) | 2001-01-16 |
| JP4408578B2 (en) | 2010-02-03 |
| EP1116719A3 (en) | 2001-10-24 |
| US6515147B2 (en) | 2003-02-04 |
| NO327039B1 (en) | 2009-04-06 |
| CN1306000A (en) | 2001-08-01 |
| KR100788529B1 (en) | 2007-12-24 |
| CN1204133C (en) | 2005-06-01 |
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