IE56385B1 - Dihydropyridine intermediate - Google Patents
Dihydropyridine intermediateInfo
- Publication number
- IE56385B1 IE56385B1 IE2240/85A IE224085A IE56385B1 IE 56385 B1 IE56385 B1 IE 56385B1 IE 2240/85 A IE2240/85 A IE 2240/85A IE 224085 A IE224085 A IE 224085A IE 56385 B1 IE56385 B1 IE 56385B1
- Authority
- IE
- Ireland
- Prior art keywords
- preparation
- chloro
- dihydropyridine
- ethoxycarbonyl
- aminoethoxymethyl
- Prior art date
Links
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 title claims 2
- 238000002360 preparation method Methods 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 4
- -1 2-Aminoethoxymethyl Chemical group 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- DGRVQOKCSKDWIH-UHFFFAOYSA-N 1-chloro-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1Cl DGRVQOKCSKDWIH-UHFFFAOYSA-N 0.000 description 1
- KUNCMOAFNYLOSC-UHFFFAOYSA-N 2-chloro-3-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(C=O)=C1Cl KUNCMOAFNYLOSC-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Preparation of 2-(2-aminoethoxymethyl)-4-(2-chloro’-3-trifluorogiethylphenyl)-3-ethoxycarbonyl-5-methoxycarbony3-6-methyl-l ,4-
The phthalimido compound from Preparation 1 (2.8 g) was added to aqueous methylamine (14 ml of 40Z) and stirred at room temperature for 17 hours· The resultant solid was filtered, redissolved In chloroform (50 ml), dried (MgSO*), filtered and evaporated to give a yellow solid. Crystallisation from hexane gave the title compound, yield 1.0 g, m.p. 122°.
Analysis:Found: C.53.25; H.4.9; N.5.75
Calculated fron c2l^24C1F3V2°5: C,52.9; H.5.1; N.5.9.
Exacrcle 2
--Preparation of 2-i2-Amlnoethpxymet.hyl]-4-(2-chloro-3-trifluorpme thylpheny 1)-3-e t hoxycarbony 1-5-me thoxy car bony 3-6-methyl
1,4-dlhydropyridine
The title compound was prepared by the catalytic hydrogenation of the azido compound of Preparation 2 by the method described In Preparation 1 of Patent Specification No.
This compound was confirmed by n.m.r. and l.r. analysis 5 to be Identical to the product of Example 1 above.
The following preparations describe the preparation of certain starting materials.
PREPARATION I
The following compound, m.p. 179%, was prepared similarly to 10 Preparation 5 of the said Patent Specification No. 30/0^3 but using 2-chloro-3-trifluoromethylbenzaJdehyde In stage (11). The
Analysis:
Found: C.57.2; H.4.45; N.4.8%;
Calculated for C^H^ClF^Oy.· C.57.4; H.4.3; N.4.6%.
PREPARATION 2
Preparation of 2-(2-azidoethoxyiBethyl)-4-(2-chloro-3-trlfluoronethylpheny l)-3-ethoxycarbonyl-5-methoxycarbonyl-6-Bethyl-l ,4dl hydropyridine
The title compound, m.p. 143-145°C, was prepared similarly to the method described In Preparation 3 of the said Patent Specification No. but using 2-chloro-3-trifluoromethylbenzaldehyde. The reaction time was the same;10
Analysis:Found:
Calculated for c2iH22ClF3N4°5:
C,50.2; H,4.4; N,11.3%; 0,50.15; H.4.4; N,ll.l%.
PREPARATION 3
Preparation of 2-chloro-3-trlfluoromethylbenzaldehyde 15 2-Chloro-l-trifluoromethylbenzene (54.15 g) was dissolved In dry tetrahydrofuran (500 ml) and stirred while cooling to -68° C under a stream of dry nitrogen. (The whole reaction Is carried out under dry nitrogen until the addition of distilled water.) -To this vas added n-butyl lithium (180 ml of 1.6 M solution in hexane) dropwlse keeping the temperature below -60°C. After stirring at-68°c for a further 2 hours, a solution of dimethylformamide (22 ml) in dry tetrahydrofuran (100 al) vas added dropwise keeping the temperature below -60° C. The reaction mixture was allowed to warm to room temperature slowly over 17 hours and distilled water (200 ml) was then added. The organic phase vas separated off and the aqueous liquors were extracted with ether (100 ml). The combined ether extracts plus the organic phase were washed with saturated brine, dried filtered and evaporated to give 61.5 g of an orange oil, being the crude title compound.
This oil vas then added to an aqueous sodiua bisulphite solution (65 g in 600 ml distilled water) and heated at 60° C for 0.5 hours. The solution was extracted with methylene chloride (3 x 100ml) and, after acidification of the aqueous phase with concentrated sulphuric acid to pH<=-|, was heated at 100°C for a further 0.5 hours. The resultant aqueous solution was extracted with methylene, chloride (3 x 200 al) and the combined organic extracts were dried (MgSO*), filtered and evaporated to give 42 g of a colourless solid which was crystallised from hexane to give the title compound, m.p. 43-44°C.
Analysis:
Found: C.45.9; H,2.0%;
Calculated for CgH^ClO: C.46.1; H,2.0%.
Claims (6)
- CLAIMS 3 . 3. 4. 4.
- 2-(2-Aninoethoxymethyl)-4-(2-chloro-
- 3-trifluorone thy Iphenyl) -3-ethoxycarbonyl-5-nethoxycarbonyl-6-Bethyl-i .4dihydropyridine. A pharmaceutical composition comprising the compound as claimed in Claim 1 in association with a pharmaceutically acceptable carrier or diluent therefor. A process for the preparation of 2-(2-aminoethoxymethyl)
- 4- (2-ch2 oro-3-trif luoromethylphenyl) -3-ethoxycarbcnyl
- 5- methoxycarbonyl -
- 6-methy 1-1,4-dihydropyridine, substantially ashereinbefore described and exemplified. 2. - (2-Aminoethoxymethyl) -4- (2-chloro-3-trif luoromethylphenvl) -3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl1,4-dihydropyridine whenever prepared by the process claimed in Claim 3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE2240/85A IE56385B1 (en) | 1983-12-20 | 1983-12-20 | Dihydropyridine intermediate |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE2240/85A IE56385B1 (en) | 1983-12-20 | 1983-12-20 | Dihydropyridine intermediate |
| IE3010/83A IE56384B1 (en) | 1982-12-21 | 1983-12-20 | Dihydropyridines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IE56385B1 true IE56385B1 (en) | 1991-07-17 |
Family
ID=11037424
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2240/85A IE56385B1 (en) | 1983-12-20 | 1983-12-20 | Dihydropyridine intermediate |
Country Status (1)
| Country | Link |
|---|---|
| IE (1) | IE56385B1 (en) |
-
1983
- 1983-12-20 IE IE2240/85A patent/IE56385B1/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |