GB1571990A - Process for the preparation of cyanoacetic acid anilide derivatives - Google Patents
Process for the preparation of cyanoacetic acid anilide derivatives Download PDFInfo
- Publication number
- GB1571990A GB1571990A GB51910/76A GB5191076A GB1571990A GB 1571990 A GB1571990 A GB 1571990A GB 51910/76 A GB51910/76 A GB 51910/76A GB 5191076 A GB5191076 A GB 5191076A GB 1571990 A GB1571990 A GB 1571990A
- Authority
- GB
- United Kingdom
- Prior art keywords
- general formula
- acid
- cyanoacetic acid
- group
- mixture
- 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.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 105
- XCTQPMCULSZKLT-UHFFFAOYSA-N 2-cyano-n-phenylacetamide Chemical class N#CCC(=O)NC1=CC=CC=C1 XCTQPMCULSZKLT-UHFFFAOYSA-N 0.000 title claims description 28
- 238000002360 preparation method Methods 0.000 title description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 70
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- GLPCMJHDPXSCPC-UHFFFAOYSA-N 2-cyano-4-hydroxy-n-phenylbut-2-enamide Chemical class OCC=C(C#N)C(=O)NC1=CC=CC=C1 GLPCMJHDPXSCPC-UHFFFAOYSA-N 0.000 claims abstract description 14
- OPXYNEYEDHAXOM-UHFFFAOYSA-N 3-oxobutanenitrile Chemical compound CC(=O)CC#N OPXYNEYEDHAXOM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000012948 isocyanate Substances 0.000 claims abstract description 7
- 150000002513 isocyanates Chemical class 0.000 claims abstract description 7
- -1 acetic acid halide Chemical class 0.000 claims description 58
- 239000002904 solvent Substances 0.000 claims description 58
- 239000002253 acid Substances 0.000 claims description 38
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 32
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 29
- 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 28
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 229910052708 sodium Inorganic materials 0.000 claims description 22
- 150000007514 bases Chemical class 0.000 claims description 20
- 239000011734 sodium Substances 0.000 claims description 20
- 150000003931 anilides Chemical class 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 17
- 239000011541 reaction mixture Substances 0.000 claims description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- 239000003085 diluting agent Substances 0.000 claims description 15
- 150000003512 tertiary amines Chemical class 0.000 claims description 15
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 14
- 229910052700 potassium Inorganic materials 0.000 claims description 14
- 229910000027 potassium carbonate Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 239000011591 potassium Substances 0.000 claims description 12
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 230000007935 neutral effect Effects 0.000 claims description 7
- 239000012312 sodium hydride Substances 0.000 claims description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 6
- DYRDKSSFIWVSNM-UHFFFAOYSA-N acetoacetanilide Chemical compound CC(=O)CC(=O)NC1=CC=CC=C1 DYRDKSSFIWVSNM-UHFFFAOYSA-N 0.000 claims description 6
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 6
- 150000002168 ethanoic acid esters Chemical class 0.000 claims description 6
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 claims description 6
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 6
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical group CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 claims description 5
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 4
- 239000000010 aprotic solvent Substances 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- IPBVNPXQWQGGJP-UHFFFAOYSA-N phenyl acetate Chemical compound CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 claims description 4
- ZFPGARUNNKGOBB-UHFFFAOYSA-N 1-Ethyl-2-pyrrolidinone Chemical compound CCN1CCCC1=O ZFPGARUNNKGOBB-UHFFFAOYSA-N 0.000 claims description 3
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 claims description 3
- 239000002841 Lewis acid Substances 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 125000005521 carbonamide group Chemical group 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- BUXTXUBQAKIQKS-UHFFFAOYSA-N sulfuryl diisocyanate Chemical compound O=C=NS(=O)(=O)N=C=O BUXTXUBQAKIQKS-UHFFFAOYSA-N 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 239000012345 acetylating agent Substances 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 6
- 230000001760 anti-analgesic effect Effects 0.000 abstract description 5
- 230000000507 anthelmentic effect Effects 0.000 abstract description 2
- 230000001857 anti-mycotic effect Effects 0.000 abstract description 2
- 239000002543 antimycotic Substances 0.000 abstract description 2
- 230000000855 fungicidal effect Effects 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
- 239000000203 mixture Substances 0.000 description 112
- 239000000243 solution Substances 0.000 description 81
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 75
- 238000002844 melting Methods 0.000 description 75
- 230000008018 melting Effects 0.000 description 75
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 58
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 42
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
- 239000002244 precipitate Substances 0.000 description 30
- 238000003756 stirring Methods 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 235000015424 sodium Nutrition 0.000 description 24
- 239000000126 substance Substances 0.000 description 21
- 239000002585 base Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- UXAGBBWETXVJBA-UHFFFAOYSA-N 2-cyano-4-hydroxy-N-[3-(trifluoromethyl)phenyl]but-2-enamide Chemical compound FC(C=1C=C(NC(C(C#N)=CCO)=O)C=CC=1)(F)F UXAGBBWETXVJBA-UHFFFAOYSA-N 0.000 description 19
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
- 235000019441 ethanol Nutrition 0.000 description 19
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 18
- 238000006640 acetylation reaction Methods 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 230000021736 acetylation Effects 0.000 description 14
- 229940093499 ethyl acetate Drugs 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- 239000001257 hydrogen Substances 0.000 description 14
- GSQPDTMXQHEJRH-UHFFFAOYSA-N N-(3-chlorophenyl)-2-cyano-4-hydroxybut-2-enamide Chemical compound ClC=1C=C(C=CC1)NC(C(C#N)=CCO)=O GSQPDTMXQHEJRH-UHFFFAOYSA-N 0.000 description 13
- MLIREBYILWEBDM-UHFFFAOYSA-N anhydrous cyanoacetic acid Natural products OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 13
- 238000001035 drying Methods 0.000 description 13
- 238000001704 evaporation Methods 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 229910052783 alkali metal Inorganic materials 0.000 description 12
- 230000007062 hydrolysis Effects 0.000 description 12
- 238000006460 hydrolysis reaction Methods 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- ORLZOZCULIRPFA-UHFFFAOYSA-N 2-cyano-4-hydroxybut-2-enoic acid Chemical compound OCC=C(C#N)C(O)=O ORLZOZCULIRPFA-UHFFFAOYSA-N 0.000 description 11
- 235000007686 potassium Nutrition 0.000 description 11
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- 235000011121 sodium hydroxide Nutrition 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000003513 alkali Substances 0.000 description 10
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 238000001953 recrystallisation Methods 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 9
- 238000009835 boiling Methods 0.000 description 9
- 239000007795 chemical reaction product Substances 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- DFPGMWQFUCNAJN-UHFFFAOYSA-N BrC=1C=C(NC(C(C#N)=CCO)=O)C=CC1 Chemical compound BrC=1C=C(NC(C(C#N)=CCO)=O)C=CC1 DFPGMWQFUCNAJN-UHFFFAOYSA-N 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- JHGKLDZJAHYJIP-UHFFFAOYSA-N n-(3-chlorophenyl)-2-cyanoacetamide Chemical compound ClC1=CC=CC(NC(=O)CC#N)=C1 JHGKLDZJAHYJIP-UHFFFAOYSA-N 0.000 description 8
- 239000012053 oil suspension Substances 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 230000035484 reaction time Effects 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000012346 acetyl chloride Substances 0.000 description 7
- 150000001298 alcohols Chemical class 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 235000011181 potassium carbonates Nutrition 0.000 description 7
- RMPAZFSYXHPNDW-UHFFFAOYSA-N 2-cyano-3-hydroxy-n-phenylbut-2-enamide Chemical class CC(O)=C(C#N)C(=O)NC1=CC=CC=C1 RMPAZFSYXHPNDW-UHFFFAOYSA-N 0.000 description 6
- MMIBXTBUKIFQAR-UHFFFAOYSA-N C1=CC(=CC=C1NC(=O)C(=CCO)C#N)Br Chemical compound C1=CC(=CC=C1NC(=O)C(=CCO)C#N)Br MMIBXTBUKIFQAR-UHFFFAOYSA-N 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 6
- 150000001340 alkali metals Chemical class 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 229910052749 magnesium Inorganic materials 0.000 description 6
- 235000015320 potassium carbonate Nutrition 0.000 description 6
- 239000000376 reactant Substances 0.000 description 6
- 229950011008 tetrachloroethylene Drugs 0.000 description 6
- 229940086542 triethylamine Drugs 0.000 description 6
- HYPXSLNQQNLJDY-UHFFFAOYSA-N 2-cyano-n-[3-(trifluoromethyl)phenyl]acetamide Chemical compound FC(F)(F)C1=CC=CC(NC(=O)CC#N)=C1 HYPXSLNQQNLJDY-UHFFFAOYSA-N 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 5
- YWJVUOTVKRDVPF-UHFFFAOYSA-N CCOCC=C(C#N)C(=O)NC1=CC(=CC=C1)Cl Chemical compound CCOCC=C(C#N)C(=O)NC1=CC(=CC=C1)Cl YWJVUOTVKRDVPF-UHFFFAOYSA-N 0.000 description 5
- TTYYGTYPWGNGIQ-UHFFFAOYSA-N FC1=CC=C(NC(C(C#N)=CCO)=O)C=C1 Chemical compound FC1=CC=C(NC(C(C#N)=CCO)=O)C=C1 TTYYGTYPWGNGIQ-UHFFFAOYSA-N 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 5
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 5
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 5
- 150000001448 anilines Chemical class 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 5
- WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 235000001055 magnesium Nutrition 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 239000006286 aqueous extract Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- 230000020477 pH reduction Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- DEAGCAOJVRQUPK-UHFFFAOYSA-N 2-cyano-3-oxobutanoic acid Chemical class CC(=O)C(C#N)C(O)=O DEAGCAOJVRQUPK-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- ZCOMHBIIMHDTAE-UHFFFAOYSA-N CC(C=CC(Cl)=C1)=C1NC(C(C#N)=CCO)=O Chemical compound CC(C=CC(Cl)=C1)=C1NC(C(C#N)=CCO)=O ZCOMHBIIMHDTAE-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001342 alkaline earth metals Chemical class 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
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- WOWBFOBYOAGEEA-UHFFFAOYSA-N diafenthiuron Chemical compound CC(C)C1=C(NC(=S)NC(C)(C)C)C(C(C)C)=CC(OC=2C=CC=CC=2)=C1 WOWBFOBYOAGEEA-UHFFFAOYSA-N 0.000 description 1
- 150000004816 dichlorobenzenes Chemical class 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 159000000014 iron salts Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 235000012254 magnesium hydroxide Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- 229910000372 mercury(II) sulfate Inorganic materials 0.000 description 1
- ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- IBHCCLKPASINHW-UHFFFAOYSA-N n-(2-bromophenyl)-2-cyanoacetamide Chemical compound BrC1=CC=CC=C1NC(=O)CC#N IBHCCLKPASINHW-UHFFFAOYSA-N 0.000 description 1
- OJUWEMQIWPEFNO-UHFFFAOYSA-N n-(3-bromophenyl)-2-cyanoacetamide Chemical compound BrC1=CC=CC(NC(=O)CC#N)=C1 OJUWEMQIWPEFNO-UHFFFAOYSA-N 0.000 description 1
- MTPKMGABYQNMMG-UHFFFAOYSA-N n-(3-chlorophenyl)-3-oxobutanamide Chemical compound CC(=O)CC(=O)NC1=CC=CC(Cl)=C1 MTPKMGABYQNMMG-UHFFFAOYSA-N 0.000 description 1
- PCGMZJHAOYYUHF-UHFFFAOYSA-N n-(4-fluorophenyl)-3-oxobutanamide Chemical compound CC(=O)CC(=O)NC1=CC=C(F)C=C1 PCGMZJHAOYYUHF-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- BFNYNEMRWHFIMR-UHFFFAOYSA-N tert-butyl 2-cyanoacetate Chemical class CC(C)(C)OC(=O)CC#N BFNYNEMRWHFIMR-UHFFFAOYSA-N 0.000 description 1
- 150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 239000011686 zinc sulphate Substances 0.000 description 1
- 235000009529 zinc sulphate Nutrition 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
- C07D317/66—Nitrogen atoms not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Pain & Pain Management (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752555685 DE2555685A1 (de) | 1975-12-11 | 1975-12-11 | Neue cyanessigsaeureanilid-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
| DE19752557003 DE2557003A1 (de) | 1975-12-18 | 1975-12-18 | Neue cyanessigsaeureanilid-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1571990A true GB1571990A (en) | 1980-07-23 |
Family
ID=25769723
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB51910/76A Expired GB1571990A (en) | 1975-12-11 | 1976-12-13 | Process for the preparation of cyanoacetic acid anilide derivatives |
Country Status (12)
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0257882A1 (en) * | 1986-08-08 | 1988-03-02 | Lilly Industries Limited | N-Phenyl butenamides with pharmaceutical properties |
| EP0259972A3 (en) * | 1986-08-08 | 1990-05-02 | Lilly Industries Limited | Heterocyclic propene amide derivatives, processes for their preparation and their use as pharmaceuticals |
| WO2000056703A1 (en) * | 1999-03-19 | 2000-09-28 | Parker Hughes Institute | Inhibitors of the egf-receptor tyrosine kinase and their use |
| WO2010013159A1 (en) * | 2008-07-29 | 2010-02-04 | Alembic Limited | A process for the preparation of teriflunomide |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0088545B1 (en) * | 1982-03-05 | 1985-12-11 | Fbc Limited | Fungicidal cyanopropenoates and compositions containing them |
| DE3534440A1 (de) * | 1985-09-27 | 1987-04-02 | Hoechst Ag | Arzneimittel gegen chronische graft-versus-host-krankheiten sowie gegen autoimmunerkrankungen, insbesondere systemischen lupus erythematodes |
-
1976
- 1976-12-03 DK DK545976A patent/DK545976A/da not_active Application Discontinuation
- 1976-12-04 ES ES453963A patent/ES453963A2/es not_active Expired
- 1976-12-06 NL NL7613547A patent/NL7613547A/xx not_active Application Discontinuation
- 1976-12-09 LU LU76354A patent/LU76354A1/xx unknown
- 1976-12-09 IT IT30233/76A patent/IT1124789B/it active
- 1976-12-10 CH CH1560476A patent/CH632487A5/de not_active IP Right Cessation
- 1976-12-10 CA CA267,670A patent/CA1092133A/en not_active Expired
- 1976-12-10 IE IE2706/76A patent/IE44047B1/en unknown
- 1976-12-10 MX MX765215U patent/MX4758E/es unknown
- 1976-12-11 JP JP51148336A patent/JPS5273830A/ja active Pending
- 1976-12-13 GB GB51910/76A patent/GB1571990A/en not_active Expired
- 1976-12-13 FR FR7637514A patent/FR2334350A2/fr active Granted
-
1978
- 1978-02-01 ES ES466542A patent/ES466542A2/es not_active Expired
- 1978-11-15 ES ES475109A patent/ES475109A1/es not_active Expired
- 1978-11-15 ES ES475111A patent/ES475111A1/es not_active Expired
- 1978-11-15 ES ES475110A patent/ES475110A1/es not_active Expired
- 1978-11-15 ES ES475108A patent/ES475108A2/es not_active Expired
-
1981
- 1981-04-14 CH CH250681A patent/CH630342A5/de not_active IP Right Cessation
- 1981-04-14 CH CH250881A patent/CH629757A5/de not_active IP Right Cessation
- 1981-04-14 CH CH250481A patent/CH630341A5/de not_active IP Right Cessation
- 1981-04-14 CH CH250781A patent/CH629756A5/de not_active IP Right Cessation
- 1981-04-14 CH CH250581A patent/CH629755A5/de not_active IP Right Cessation
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0257882A1 (en) * | 1986-08-08 | 1988-03-02 | Lilly Industries Limited | N-Phenyl butenamides with pharmaceutical properties |
| US4892963A (en) * | 1986-08-08 | 1990-01-09 | Lilly Industries Limited | N-phenyl amide compounds |
| EP0259972A3 (en) * | 1986-08-08 | 1990-05-02 | Lilly Industries Limited | Heterocyclic propene amide derivatives, processes for their preparation and their use as pharmaceuticals |
| US4983619A (en) * | 1986-08-08 | 1991-01-08 | Lilly Industries Limited | Pharmaceutical compounds |
| US6355678B1 (en) | 1998-06-29 | 2002-03-12 | Parker Hughes Institute | Inhibitors of the EGF-receptor tyrosine kinase and methods for their use |
| US6864286B2 (en) | 1998-06-29 | 2005-03-08 | Parker Hughes Institute | Inhibitors of the EGF-receptor tyrosine kinase and methods for their use |
| WO2000056703A1 (en) * | 1999-03-19 | 2000-09-28 | Parker Hughes Institute | Inhibitors of the egf-receptor tyrosine kinase and their use |
| WO2010013159A1 (en) * | 2008-07-29 | 2010-02-04 | Alembic Limited | A process for the preparation of teriflunomide |
| US8420856B2 (en) | 2008-07-29 | 2013-04-16 | Alembic Ltd. | Process for preparation of teriflunomide |
Also Published As
| Publication number | Publication date |
|---|---|
| DK545976A (da) | 1977-06-12 |
| MX4758E (es) | 1982-09-03 |
| ES475108A2 (es) | 1979-08-01 |
| CH629756A5 (en) | 1982-05-14 |
| CA1092133A (en) | 1980-12-23 |
| CH629755A5 (en) | 1982-05-14 |
| IE44047L (en) | 1977-06-11 |
| ES475110A1 (es) | 1979-05-01 |
| NL7613547A (nl) | 1977-06-14 |
| FR2334350B2 (enrdf_load_stackoverflow) | 1980-03-07 |
| CH630342A5 (en) | 1982-06-15 |
| JPS5273830A (en) | 1977-06-21 |
| CH632487A5 (en) | 1982-10-15 |
| ES466542A2 (es) | 1979-01-16 |
| CH629757A5 (en) | 1982-05-14 |
| ES453963A2 (es) | 1978-05-01 |
| CH630341A5 (en) | 1982-06-15 |
| LU76354A1 (enrdf_load_stackoverflow) | 1977-06-24 |
| ES475109A1 (es) | 1979-04-16 |
| ES475111A1 (es) | 1979-05-01 |
| IE44047B1 (en) | 1981-07-29 |
| FR2334350A2 (fr) | 1977-07-08 |
| IT1124789B (it) | 1986-05-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed | ||
| PE20 | Patent expired after termination of 20 years |
Effective date: 19960606 |