IE58522B1 - 6-substituted-furo-(3,4-c)-pyridine derivatives - Google Patents
6-substituted-furo-(3,4-c)-pyridine derivativesInfo
- Publication number
- IE58522B1 IE58522B1 IE214385A IE214385A IE58522B1 IE 58522 B1 IE58522 B1 IE 58522B1 IE 214385 A IE214385 A IE 214385A IE 214385 A IE214385 A IE 214385A IE 58522 B1 IE58522 B1 IE 58522B1
- Authority
- IE
- Ireland
- Prior art keywords
- hydroxy
- furo
- dihydro
- pyridine
- yield
- Prior art date
Links
- -1 6-substituted-furo-(3,4-c)-pyridine Chemical class 0.000 title abstract description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000012454 non-polar solvent Substances 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 29
- 238000002360 preparation method Methods 0.000 claims description 7
- KEKQEYBOTHGIGL-UHFFFAOYSA-N 7-hydroxyfuro[3,4-c]pyridine-6-carbaldehyde Chemical class C(=O)C1=C(C=2C(C=N1)=COC2)O KEKQEYBOTHGIGL-UHFFFAOYSA-N 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 abstract description 9
- 208000004880 Polyuria Diseases 0.000 abstract description 2
- AVZNLXBMQVKETP-UHFFFAOYSA-M [Br-].CN(C)CC([Mg+])=C Chemical compound [Br-].CN(C)CC([Mg+])=C AVZNLXBMQVKETP-UHFFFAOYSA-M 0.000 abstract description 2
- 239000000739 antihistaminic agent Substances 0.000 abstract description 2
- 229940125715 antihistaminic agent Drugs 0.000 abstract description 2
- 230000036772 blood pressure Effects 0.000 abstract description 2
- 229910052801 chlorine Inorganic materials 0.000 abstract description 2
- 230000035619 diuresis Effects 0.000 abstract description 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 2
- 210000003734 kidney Anatomy 0.000 abstract description 2
- 125000003884 phenylalkyl group Chemical group 0.000 abstract description 2
- 125000006413 ring segment Chemical group 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 20
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- 238000000354 decomposition reaction Methods 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 238000003756 stirring Methods 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- CXFIWPAUNODACX-KQQUZDAGSA-N 4-[(1e,3e)-4-[4-(dimethylamino)phenyl]buta-1,3-dienyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1\C=C\C=C\C1=CC=C(N(C)C)C=C1 CXFIWPAUNODACX-KQQUZDAGSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- FSAIGSHOZKOJHJ-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-ylmethyl)-3,4-dihydro-1h-isoquinoline Chemical compound C1CC2=CC=CC=C2CN1CN1CC2=CC=CC=C2CC1 FSAIGSHOZKOJHJ-UHFFFAOYSA-N 0.000 description 1
- PJAFKGLPUVYSMP-UHFFFAOYSA-N 3-(4-chlorophenyl)-7-hydroxy-1,3-dihydrofuro[3,4-c]pyridine-6-carbaldehyde Chemical compound ClC1=CC=C(C=C1)C1OCC2=C1C=NC(=C2O)C=O PJAFKGLPUVYSMP-UHFFFAOYSA-N 0.000 description 1
- JZYREUZTIFGONP-UHFFFAOYSA-N 3-(4-fluorophenyl)-7-hydroxy-1,3-dihydrofuro[3,4-c]pyridine-6-carbaldehyde Chemical compound FC1=CC=C(C=C1)C1OCC2=C1C=NC(=C2O)C=O JZYREUZTIFGONP-UHFFFAOYSA-N 0.000 description 1
- BFJMHTOBRRZELQ-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C(I)=NNC2=C1 BFJMHTOBRRZELQ-UHFFFAOYSA-N 0.000 description 1
- NJKUKUIJCBTUAG-UHFFFAOYSA-N 7-hydroxy-3-methyl-3-pentyl-1H-furo[3,4-c]pyridine-6-carbaldehyde Chemical compound CC1(OCC2=C1C=NC(=C2O)C=O)CCCCC NJKUKUIJCBTUAG-UHFFFAOYSA-N 0.000 description 1
- LSHYFUDECLDRPE-UHFFFAOYSA-N 7-hydroxy-3-methyl-3-phenyl-1H-furo[3,4-c]pyridine-6-carbaldehyde Chemical compound CC1(OCC2=C1C=NC(=C2O)C=O)C2=CC=CC=C2 LSHYFUDECLDRPE-UHFFFAOYSA-N 0.000 description 1
- NPGWFLVNYKKUMM-UHFFFAOYSA-N 7-hydroxy-3-phenyl-1,3-dihydrofuro[3,4-c]pyridine-6-carbaldehyde Chemical compound C1(=CC=CC=C1)C1OCC2=C1C=NC(=C2O)C=O NPGWFLVNYKKUMM-UHFFFAOYSA-N 0.000 description 1
- SFZWBIOZTWKZHS-UHFFFAOYSA-N 7-hydroxy-3-propyl-1,3-dihydrofuro[3,4-c]pyridine-6-carbaldehyde Chemical compound C(CC)C1OCC2=C1C=NC(=C2O)C=O SFZWBIOZTWKZHS-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- SVPQRBCSONEAHF-UHFFFAOYSA-N ac1mxsc9 Chemical compound C1CCCCC1N=C1C=C2N3C(CCCC4)=C4CC4CCCCC43N=C2C=C1 SVPQRBCSONEAHF-UHFFFAOYSA-N 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000006229 carbon black Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000004984 dialkylaminoalkoxy group Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- BIRWRIAEWIXFHT-UHFFFAOYSA-N furo[3,4-c]pyridin-7-ol Chemical compound OC1=CN=CC2=COC=C12 BIRWRIAEWIXFHT-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000002734 organomagnesium group Chemical group 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Abstract
The compounds I (A1, A2 independently = H, C1-C5hydrocarbon, heterocycle up to 6 ring atoms, carbomonocycle, phenylalkyl, phenylalkenyl; each (except H) unsubstituted or substituted by one or more of F, Cl, CF3, C1-C5alkyl, C1-C5alkoxy, C1-C5alkylthio, di(C1-C5alkyl)-amino, di(C1-C5alkyl)-amino- (C1-C5alkoxy), alpha - or beta -(C1-C5alkoxy)-N-pyrrolidinyl), which are known compounds of interest for their therapeutical activity, principally in the fields of diuresis, lowering of blood pressure, kidney protection and also as antihistaminic agents, are prepared by reacting the corresponding 6-formyl derivatives with 1- dimethylaminomethyl-vinylmagnesium bromide at the boil in a non-polar solvent such as tetrahydrofuran.
Description
The invention relates to the preparation of 1,3-dihydro-6-(l-hydroxy-2dimethylaminomethyl-ally 1) -7-hydroxy-furo -{3,4-c)-pyridine derivatives of the general formula I h3c h3c N— CH, wherein each of A^ and A2 independently represents a hydrogen atom, a straight chain saturated or unsaturated hydrocarbon group having from 1 to 5 carbon atoms, a heterocyclic group having up to 6 ring atoms, a carbomonocyclic group, a phenylalkyl group or a phenylalkenyl group, each of the groups represented by A^ and A2 being unsubstituted or being substituted by one or more chlorine or fluorine atoms, trifluoromethyl groups, alkyl groups having from 1 to 5 carbon atoms, alkoxy groups having from 1 to 5 carbon atoms, alkylthio groups having from 1 to 5 carbon atoms, dialkylamino groups in which each alkyl group has from 1 to 5 carbon atoms, dialkylaminoalkoxy groups in which each of the two alkyl groups and the alkoxy group has from 1 to 5 carbon atoms or a or β - (N-pyrrolidinyl.)-alkoxy groups in which the alkoxy group has from 1 to 5 carbon atoms. - 2 These compounds have been described and claimed in our British Patent Specification No. 2,153,824 corresponding to Irish Patent Application No. 241/85. They are of interest for their therapeutical activity, principally in the fields of diuresis, lowering of blood pressure, kidney protection and also as antihistaminic agents.
It has surprisingly been found that in the process described in our aforesaid Irish Patent Application the protection of the hydroxy group in position 7 might be omitted and nevertheless the product might be prepared with a better yield.
Accordingly, the invention provides a process for the preparation of 1,3-d i hydro-6-(1-hydroxy-2-dimethy1 ami no-methyl-a1ly1)-7-hydroxy-furo(3,4-c)-pyridine derivatives of the general formula I as above defined, the process comprising reacting a 6-formyl-7-hydroxy-furo-(3,4-c)pyridine derivative of the general formula II wherein A^ and A2 are as above defined with a slight excess of 1-dimethylaminomethyl-vinylmagnesium bromide at the boil, in a non polar solvent such as tetrahydrofuran.
The 6-formyl-7-hydroxy-furo-(3,4-c)-pyridine derivatives II may be obtained from corresponding 6-methyl-7-hydroxy derivatives of the general formula III wherein A^ and A2 are as above defined by the following sequence of reactions: HO MnO2 -> The compounds III are disclosed in our Irish Patent Application Nos. 288/82 and 826/84. - 4 The preparation of one only of the starting compounds, 1.3- dihydro-3-p-chlorophenyl-6-formy1-7-hydroxy-furo-(3,4-c) pyridine, is now described in detail, other starting materials being obtained by the same way. a) Into a one litre reactor fitted with stirring, warming and cooling means, 22.3 g of 1.3- dihydro-3-p-chlorophenyl-6- methyl -7-hydroxy-furo-(3,4-c)pyridine were treated at 0°C, in the presence of 300 ml of methylene dichloride, with 18.2 g of m-peroxybenzoic acid, slowly added. After stirring overnight at room temperature, there were added 150 ml of 10 % sodium sulphate solution.
After stirring and decantation, the methylene dichloride phase was washed with the same amount of sodium sulphate solution, twice with 150 ml of sodium bicarbonate solution and three times with 100 ml of water then dried over anhydrous sodium sulphate. By evaporation to dryness, there was obtained a beige precipitate which was washed with petroleum ether, filtered and dried. Yield 22.9 g (96 %) of 1.3- dihydro-3-p-chlorophenyl-6-methyl-7-hydroxy -furo-(3,4-c) pyridine-N-oxide. b) In the same reactor as above, the 22.9 g of the compound obtained in the previous step were treated at 0-5°C, in the presence of 175 ml of methylene dichloride, with 4.3 ml of trifluoroacetic anhydride added dropwise under stirring. The mixture was stirred overnight at room temperature, and then cooled and treated dropwise with 95 ml of methanol. After evaporation to dryness, the residue was taken up in 300 ml of chloroform, washed twice with 75 ml of 10 % sodium bicarbonate solution and three times with 100 ml of water and dried on anhydrous sodium sulphate. The chloroform was evaporated off and the residue was washed with diethyl ether and dried under reduced pressure. Yield 21.3 g (93 %) of l,3-dihydro-3-pchlorophenyl-6-hydroxymethyl-7-hydroxy-furo-(3,4-c)-pyr idine. - 5 c) The 21.3 g of the compound obtained in the previous step were treated in a 2 litre reactor with 27 g of manganese dioxide in the presence of 0.9 litre of chloroform at 28-30°C under stirring for 3 hours. After separation, filtration, washing with chloroform and then with ethyl acetate, the solution was evaporated to dryness and the paste treated with isopropyl oxide then with pentane. There was thus obtained 20.1 g (95 %) of 1,3-dihydro-3-p-chlorophenyl-6-formyl-7hydroxy-furo-(3,4- c)-pyridine.
The following examples illustrate the invention.
Example 1 1,3-dihydro-3-methy1-6-(1-hydroxy-2-dimethylaminomethy1-allyl) 7-hydroxy-furo-(3,4-c)-pyridine a) Preparation of the organomagnesium reagent In a two litre reactor fitted with warming, cooling and stirring means were poured, under nitrogen circulation, 19.4 g (0.8 mol) of magnesium, and 100 ml of tetrahydrofuran, preferably distilled on lithium aluminium hydride. The mixture was refluxed.
There was then slowly added 132 g (0.8 mol) of 3-dimethylamino-2-bromo-l-propylene. No external heating was applied, the reflux being maintained and controlled by the addition of this compound. At the end of the addition, one litre of distilled tetrahydrofuran was added. The mixture was refluxed for two hours and then cooled to 10°C. - 6 b) Reaction To the reaction mixture from the previous step was slowly added, under stirring, 89 g (0.5 mol) of 1 > 3-d ihydro-3-methyl-6-formyl-7-hydroxy-furo- (3,4-c) -pyi'idine. The temperature reached about 25°C at the end of the addition. Stirring was maintained overnight at room temperature. The mixture was then cooled to 0°C and 250 ml of water saturated with ammonium chloride and 250 ml of diethyl ether were added to it. After stirring for 15 minutes at room temperature there was obtained a two-phase mixture with an oil supernatant.
The mixture was separated and the aqueous phase was extracted twice with 250 ml aliquots of diethyl ether. The extracts were added to the oily phase, which had been washed with water three times. The oily phase was then dried on magnesium sulphate, treated with carbon black, concentrated to dryness and extracted twice with 250 ml of diisopropyl ether. The extracts were filtered, concentrated (reduction to 1/4 of initial volume) and cooled overnight, leading to a precipitate, which was separated and washed with diisopropyl ether. Yield 105 g (80 %).
The preparation of the other compounds of the invention follows the same process except that, in step (b), the starting material is different ; the following examples will, accordingly refer to example 1 and only mention the new starting material, the overall yield and the characteristics of the compound obtained.
Example 2 1, 3-dihydro-3-propyl-6-(l-hydroxy-2-dimethylaminomethyl-allyl·) 7-hydroxy-furo-(3,4-c)-pyr idine The method of example 1 was repeated, but starting with 83 g (0.4 mol) of 1,3-dihydro-3-propyl-6-formyl-7-hydroxyfuro-(3,4-c)-pyridine. Yield 66 % of a product melting - 7 at 187-194°C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C16H24N2°3' 2HC1Example 3 1.3- dihydro-3-cycIohexyl-6-(l-hydroxy-2-dimethylaminomethylallyl) -7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 99 g (0.4 mol) of l,3-dihydro-3-cyclohexyl-6-formyl-7hydroxy-furo-(3,4-c)-pyridine. Yield 59 % of product melting at 180-184°C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula ci9H28N2°3, 2HC1· Example 4 1.3- dihydro-3-phenyl-6-(l-hydroxy-2-d imethylaminomethyl-allyl)7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 99 g (0.4 mol) of 1,3-dihydro-3-phenyl-6-formyl-7-hydroxyfuro-(3,4-c)-pyridine. Yield 49 % of a product melting at 210-215°C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C19H22N2°3' 2HC1· Example 5 1.3- dihydro-3-p-chlorophenyl-6-(l-hydroxy-2-dimethylaminomethylallyl)-7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 110 g (0.4 mol) of l,3-dihydro-3-p-chlOrophenyl-6-formyl-7hydroxy-furo-(3,4-c)-pyridine. Yield 57 % of a product melting at 195-200°C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula c19H21clN2O3' 2HC1· 2HC1. - 8 Example 6 1,3-dihydro-3-(2,3-dichlorophenyl) -6-(1-hydroxy-2-dimethy1aminomethyl-ally1)-7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 124 g (0.4 mol) of l,3-dihydro-3-(2,3-dichloro-phenyl)-6formyl-7-hydroxy-furo-(3,4-c)-pyridine. Yield 62% °f a product melting at 180-184°C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula c19H2ocl2N2°3* 2HC1* Example 7 1.3- dihydro-3-p-fluorophenyl-6-(l-hydroxy-2-dimethylaminomethylallyl)-7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 104g (0.4 mol) of 1,3-dihydro-3-p-fluorophenyl-6-formyl-7hydroxy-furo-(3,4-c)-pyridine. Yield 62% of a product melting at 198°C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C19H21FN2°3,2HC1· Example 8 1.3- dihydro-3-p-toluyl-6-(l-hydroxy-2-dimethylaminomethylally 1) -7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 103g (0.4 mol) of l,3-dihydro-3-p-toluyl-6-formyl-7-hydroxyfuro-(3,4-c)-pyridine. Yield 66 % of a product melting at 203-207°C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C20H24N2 O3.2HC1. - 9 Example 9 1,3-d ihydro-3-p-methoxypheny1-6-(l-hydroxy-2-d ime thylaminome thyl-allyl)-7-hydroxy-furo-(3,4-c)-py ridine The method of example 1 was repeated, but starting with 110 g (0.4 mol) of l,3-dihydro-3-p-methoxyphenyl-6formyl-7-hydroxy-furo-(3,4-c)-pyridine. Yield 63% of a product melting at 169-170°C (Tottoli), the analysis of which showed a good correspondence with the formula ^20^24^^2^4- 2HC1.
Example 10 l,3-dihydro-3-m-tr ifluoromethylpheny1-6-(l-hydroxy-2-dimethy1aminomethyl-ally 1)-7-hydroxy-furo-(3,4-c)-pyr idine The method of example 1 was repeated, but starting with 124 g (0.4 mol) of l,3-dihydro-3-m-trifluoromethylphenyl-6formyl-7-hydroxy-furo-(3,4-c)-pyridine. Yield 58 % of a product melting at 217-223°C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C20H21F3N2°3* 2HC1* Example 11 1,3-dihydro-3-p-(diethylaminoethoxy-pheny1)-6-(l-hydroxy-2dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)-pyr idine The method of example 1 was repeated, but starting with 142 g (0.4 mol) of 1,3-dihydro-3-p-(diethylaminoethoxyphenyl)-6-formy1-7-hydroxy-furo-(3,4-c)-pyridine. Yield % of a product melting at 158-160°C (Tottoli) , the analysis of which showed a good correspondence with the formula C25H35N3°4- 2H<"1.
Example 12 l,3-dihydro-3-^p-jg-(N-pvrrolidinv1 )-ethoxy]-phenyj-6-(l-.hydrnxy-?dimethylaminomethyl-ally 1)-7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 142 g (0.4 mol) of l,3-dihydro-3-^p-^-(N-pyrrolidinyl)-ethoxy] phenyl^-6-formyl-7-hydroxy-furo-(3,4-c) -pyridine. Yield %) of a product melting at 173°C (Tottoli), the analysis 'i good correspondence with the formula showed 2HC1. of which C25H33N3°4 Example 13 1,3-dihydro-3-methyl-3-n-penty1-6-(l-hydroxy-2-dimethylaminomethy1-allyl)-7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 95 9 (0.4 mol) of 1,3-dihydro-3-methyl-3-n-pentyl-6-formyl-7hydroxy-furo-(3,4-c)-pyridine. Yield 59% of a product melting at 187-191°C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula ci9H30N2°3· 2hc1Example 14 1,3-d ihydro-3-methyl-3-pheny1-6-(1-hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 103 9 (0.4 mol) of 1,3-dihydro-3-methyl-3-phenyl-6-formyl-7hydroxy-furo-(3,4-c)-pyridine. Yield 69 % of a product melting at 178-179°C (Tottoli), the analysis of which showed a good correspondence with the formula C20H24N2°3- 2HC1· - U Example 15 1.3- dihydro-3-methy1-3-a -thieny1-6-(1-hydroxy-2-dimethylaminomethyl-a1lyl)-7-hydroxy-furo-(3j4-c)-pyr idine The method of example 1 was repeated, but starting with 1G3 g (0.4 mol) of 1,3-dihydro-3-methyl-3- a -thienyl-6formyl-7-hydroxy-furo-(3,4-c)-pyridine. Yield 67 % of a product melting at 169-175°C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C18H22SN2°3· 2HC1.
Example 16 1.3- dihydro-3-ethyl-3-m-tr ifluoromethyIpheny1-6-(l-hydroxy-2dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 136g {0.4 mol) of l,3-dihydro-3-ethyl-3-m-trifluoromethylphenyl-6-formy1-7-hydroxy-furo-(3,4-c)-pyridine. Yield % of a product melting at 185°C (Tottoli), the analysis of which showed a good correspondence with the formula C22H25F3N2°3· 2HCl· Example 1T_ 1,3-dihydro-3-ethyl-3- a -furyl-6-(l-hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)-pyrid ine The method of example 1 was repeated, but starting with 104 g (0.4 mol) of 1,3-dihydro-3-ethyl-3-a -furyl-6-formyl7-hydroxy-furo-(3,4-c)-pyridine. Yield 58 % of a product melting at 164-169°C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C1QHn.N„O.. 2HC1. 24 2 4 - 12 Example 18 1,3-dihydro-3-pheny1-3-p-ethoxypheny1-6-(l-hydroxy-2-dimethylaminomethyl-ally1)-7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 144 g (0.4 mol) of l,3-dihydro-3-phenyl-3-p-ethoxyphenyl-6formyl-7-hydroxy-furo-(3,4-c)-pyridine. Yield 64 % of a product melting at 148-149°C (Tottoli), the analysis of which showed a good correspondence with the formula C27H30N2°4* 2HC1.
Example 19 1,3-dihydro-3,3-di-p-fluoropheny1-6-(1-hydroxy-2-dimethylaminomethyl-ally1)-7-hydroxy-furo-(3,4-c)-pyr idine The method of example 1 was repeated, but starting with 142 g (0.4 mol) of l,3-dihydro-3,3-di-p-fluoropheny1-6formyl-7-hydroxy-furo-(3,4-c)-pyridine. Yield 70 % of a product melting at 175°C (Tottoli), the analysis of which showed a good correspondence with the formula C25H24F2N2^3’ 2HC1.
Example 20 1,3-dihydro-3-a -furyl-3-p-thiomethylphenyl-6-(l-hydroxy-2dimethylaminomethyl-ally1)-7-hydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 141 g (0.4 mol) of 1,3-dihydro-3- a -furyl-3-p-thiomethylphenyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine. Yield 48 % of a product melting at 143-151°C (Tottoli) , with decomposition, the analysis of which showed a good correspondence with the formula C24H26SN2°4* 2HC^·
Claims (4)
1. A process for the preparation of a 1,3-dihydro-6-(l-hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)-pyridine derivative having the general formula I as herein defined, the process comprising reacting a 6-formyl-7-hydroxy-furo-(3,4-c)-pyridine derivative having the general formula II as herein defined with a slight excess of l-dimethylaminomethyl-vinylmagnesium bromide at the boil, in a non polar solvent.
2. A process according to Claim 1 in which the non-polar solvent is tetrahydrofuran.
3. A process for the preparation of a 1,3-dihydro-6-(l-hydroxy-2dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)-pyridine derivative having the general formula I as herein defined, the process being substantially as described herein with reference to any of the Examples.
4. A 1,3-dihydro-6-(l-hydroxy-2-dimethylaminomethyl-allyl)-7hydroxy-furo-(3,4-c)-pyridine derivative whenever prepared by a process as claimed in any of Claims 1 to 3.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB848422029A GB8422029D0 (en) | 1984-08-31 | 1984-08-31 | 6-substituted-furo-(3 4-c)-pyridine derivatives |
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| Publication Number | Publication Date |
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| JP (1) | JPS6160688A (en) |
| AR (1) | AR241455A1 (en) |
| AT (1) | AT396590B (en) |
| BE (1) | BE903122A (en) |
| CA (1) | CA1300149C (en) |
| CH (1) | CH666688A5 (en) |
| DE (1) | DE3531004A1 (en) |
| DK (1) | DK157871C (en) |
| ES (1) | ES8604967A1 (en) |
| FI (1) | FI82468C (en) |
| FR (1) | FR2569698B1 (en) |
| GB (2) | GB8422029D0 (en) |
| HK (1) | HK6189A (en) |
| IE (1) | IE58522B1 (en) |
| IT (1) | IT1201459B (en) |
| LU (1) | LU86052A1 (en) |
| NL (1) | NL8502324A (en) |
| NO (1) | NO162071C (en) |
| OA (1) | OA08088A (en) |
| PT (1) | PT81054B (en) |
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| GB8427218D0 (en) * | 1984-10-27 | 1984-12-05 | Scras | Pyridine derivatives |
| GB8808001D0 (en) * | 1988-04-06 | 1988-05-05 | Scras | Stereospecific preparative process for furol(3,4-c)pyridine derivatives |
| DE10323602A1 (en) * | 2003-05-19 | 2004-12-16 | Südzucker AG Mannheim/Ochsenfurt | Hard caramel for human consumption, contains hard caramel base and supported food color inhomogeneously distributed within hard caramel base |
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| ZA786269B (en) * | 1977-11-25 | 1979-10-31 | Scras | New pyridine derivative,its preparation and use |
| ZA842029B (en) * | 1983-04-05 | 1984-10-31 | Scras | Furo-(3,4-c)-pyridine derivatives preparation thereof and therapeutic compositions containing the same |
| GB2153824B (en) * | 1984-02-02 | 1987-04-01 | Scras | Furo-(3,4-c)-pyridine derivatives |
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1984
- 1984-08-31 GB GB848422029A patent/GB8422029D0/en active Pending
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- 1985-08-12 ZA ZA856088A patent/ZA856088B/en unknown
- 1985-08-12 GB GB08520169A patent/GB2163744B/en not_active Expired
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