CS274285B2 - Method of substituted benzamides production - Google Patents
Method of substituted benzamides production Download PDFInfo
- Publication number
- CS274285B2 CS274285B2 CS960386A CS960386A CS274285B2 CS 274285 B2 CS274285 B2 CS 274285B2 CS 960386 A CS960386 A CS 960386A CS 960386 A CS960386 A CS 960386A CS 274285 B2 CS274285 B2 CS 274285B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- methoxy
- amino
- dihydro
- product
- filtered
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 21
- 229940054066 benzamide antipsychotics Drugs 0.000 title claims description 6
- 150000003936 benzamides Chemical class 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 102
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 65
- 239000000460 chlorine Substances 0.000 claims description 45
- 150000001875 compounds Chemical class 0.000 claims description 44
- -1 alkenyl bromide Chemical compound 0.000 claims description 43
- 229910052801 chlorine Inorganic materials 0.000 claims description 42
- 229910052794 bromium Inorganic materials 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 239000007858 starting material Substances 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 17
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 16
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- RJVBRQZYORDMGI-UHFFFAOYSA-N 5-chloro-n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-4-(4,5-dihydro-1,3-oxazol-2-ylamino)-2-methoxybenzamide Chemical compound ClC=1C=C(C(=O)NCC2N(CCC2)CC2CC2)C(OC)=CC=1NC1=NCCO1 RJVBRQZYORDMGI-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 150000003254 radicals Chemical class 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- RBGDLYUEXLWQBZ-UHFFFAOYSA-N 2-chlorobenzamide Chemical compound NC(=O)C1=CC=CC=C1Cl RBGDLYUEXLWQBZ-UHFFFAOYSA-N 0.000 claims 1
- XEQVAOQSDRCQQK-UHFFFAOYSA-N 5-chloro-4-(4,5-dihydro-1,3-thiazol-2-ylamino)-n-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxybenzamide Chemical compound CCN1CCCC1CNC(=O)C(C(=C1)OC)=CC(Cl)=C1NC1=NCCS1 XEQVAOQSDRCQQK-UHFFFAOYSA-N 0.000 claims 1
- 239000000047 product Substances 0.000 description 205
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 177
- 239000000203 mixture Substances 0.000 description 100
- 239000000243 solution Substances 0.000 description 92
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 90
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 80
- 238000002844 melting Methods 0.000 description 75
- 230000008018 melting Effects 0.000 description 75
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 64
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 239000011541 reaction mixture Substances 0.000 description 53
- 239000000463 material Substances 0.000 description 52
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- 239000000706 filtrate Substances 0.000 description 51
- 239000013078 crystal Substances 0.000 description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- 238000005406 washing Methods 0.000 description 40
- 229910052757 nitrogen Inorganic materials 0.000 description 39
- 238000004458 analytical method Methods 0.000 description 31
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 30
- 239000002244 precipitate Substances 0.000 description 30
- 238000010992 reflux Methods 0.000 description 30
- 239000002904 solvent Substances 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 26
- 238000012360 testing method Methods 0.000 description 24
- 238000003756 stirring Methods 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 20
- 238000002329 infrared spectrum Methods 0.000 description 19
- 238000000746 purification Methods 0.000 description 17
- 230000004580 weight loss Effects 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 229910021529 ammonia Inorganic materials 0.000 description 15
- 150000002148 esters Chemical class 0.000 description 15
- 238000001816 cooling Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 239000003610 charcoal Substances 0.000 description 13
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 13
- 229910000029 sodium carbonate Inorganic materials 0.000 description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 12
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 11
- 239000002178 crystalline material Substances 0.000 description 11
- 235000011837 pasties Nutrition 0.000 description 11
- 238000001228 spectrum Methods 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 239000012535 impurity Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 239000000155 melt Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- UNRBEYYLYRXYCG-UHFFFAOYSA-N (1-ethylpyrrolidin-2-yl)methanamine Chemical compound CCN1CCCC1CN UNRBEYYLYRXYCG-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 6
- 229940011051 isopropyl acetate Drugs 0.000 description 6
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000011403 purification operation Methods 0.000 description 6
- 239000012260 resinous material Substances 0.000 description 6
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 5
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 5
- 239000012065 filter cake Substances 0.000 description 5
- 230000037023 motor activity Effects 0.000 description 5
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- XVOYPIDZBJFVQY-UHFFFAOYSA-N 5-bromo-2-(carbamothioylamino)benzoic acid Chemical compound NC(=S)NC1=CC=C(Br)C=C1C(O)=O XVOYPIDZBJFVQY-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- 102000003946 Prolactin Human genes 0.000 description 4
- 108010057464 Prolactin Proteins 0.000 description 4
- HTGKTSVPJJNEMQ-QMMMGPOBSA-N [(2s)-1-prop-2-enylpyrrolidin-2-yl]methanamine Chemical compound NC[C@@H]1CCCN1CC=C HTGKTSVPJJNEMQ-QMMMGPOBSA-N 0.000 description 4
- 238000007112 amidation reaction Methods 0.000 description 4
- 230000001090 anti-dopaminergic effect Effects 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 238000010908 decantation Methods 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 229940046892 lead acetate Drugs 0.000 description 4
- VAJCUDRWSLWRBU-UHFFFAOYSA-N methyl 5-chloro-4-isothiocyanato-2-methoxybenzoate Chemical compound COC(=O)C1=CC(Cl)=C(N=C=S)C=C1OC VAJCUDRWSLWRBU-UHFFFAOYSA-N 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 229940097325 prolactin Drugs 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- JIWRGIJHCPVADK-UHFFFAOYSA-N 2-(carbamothioylamino)-5-chlorobenzoic acid Chemical compound NC(=S)Nc1ccc(Cl)cc1C(O)=O JIWRGIJHCPVADK-UHFFFAOYSA-N 0.000 description 3
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- PUVRPONDSAVLJE-UHFFFAOYSA-N [1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methanamine Chemical compound NCC1CCCN1CC1=CCCCC1 PUVRPONDSAVLJE-UHFFFAOYSA-N 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 241001515942 marmosets Species 0.000 description 3
- BFYTVABWHPEGKO-UHFFFAOYSA-N methyl 5-bromo-4-isothiocyanato-2-methoxybenzoate Chemical compound COC(=O)C1=CC(Br)=C(N=C=S)C=C1OC BFYTVABWHPEGKO-UHFFFAOYSA-N 0.000 description 3
- PQXRCOLQURVORH-UHFFFAOYSA-N methyl 5-chloro-4-(4,5-dihydro-1,3-thiazol-2-ylamino)-2-methoxybenzoate Chemical compound C1=C(OC)C(C(=O)OC)=CC(Cl)=C1NC1=NCCS1 PQXRCOLQURVORH-UHFFFAOYSA-N 0.000 description 3
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000011343 solid material Substances 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- MXHMMLVCKSZTIL-UHFFFAOYSA-N 5-chloro-n-[2-(diethylamino)ethyl]-4-(4,5-dihydro-1,3-oxazol-2-ylamino)-2-methoxybenzamide Chemical compound C1=C(OC)C(C(=O)NCCN(CC)CC)=CC(Cl)=C1NC1=NCCO1 MXHMMLVCKSZTIL-UHFFFAOYSA-N 0.000 description 2
- ZGRFCWIJQHMFEH-UHFFFAOYSA-N 5-chloro-n-[2-(diethylamino)ethyl]-4-isothiocyanato-2-methoxybenzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N=C=S)C=C1OC ZGRFCWIJQHMFEH-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 2
- 102000015554 Dopamine receptor Human genes 0.000 description 2
- 108050004812 Dopamine receptor Proteins 0.000 description 2
- 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 description 2
- 231100000111 LD50 Toxicity 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- QFIYFROFRTUSPW-UHFFFAOYSA-N [1-(cyclopropylmethyl)pyrrolidin-2-yl]methanamine Chemical compound NCC1CCCN1CC1CC1 QFIYFROFRTUSPW-UHFFFAOYSA-N 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- 230000003474 anti-emetic effect Effects 0.000 description 2
- 239000002111 antiemetic agent Substances 0.000 description 2
- 229940125683 antiemetic agent Drugs 0.000 description 2
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 2
- 229960004046 apomorphine Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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 ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- 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
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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 ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/50—Nitrogen atoms not forming part of a nitro radical with carbocyclic radicals directly attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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 ring carbon atoms
- C07D263/28—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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 ring carbon atoms
- C07D277/18—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Otolaryngology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8518829A FR2592042B1 (fr) | 1985-12-19 | 1985-12-19 | Nouveaux ortho-anisamides, leur procede d'obtention, et leurs applications therapeutiques |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS960386A2 CS960386A2 (en) | 1990-09-12 |
| CS274285B2 true CS274285B2 (en) | 1991-04-11 |
Family
ID=9325965
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS960386A CS274285B2 (en) | 1985-12-19 | 1986-12-19 | Method of substituted benzamides production |
Country Status (37)
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3782651T2 (de) * | 1987-06-17 | 1993-03-25 | Delagrange Lab | Anwendung von n-(2-(diaethylamino)aethyl)-2-methoxy-4((1-h-4,5-dihydro-2-imidazolyl)amino)-5-chlorobenzamid als anxiolytisches und antipsychotisches mittel. |
| FR2640139A1 (fr) * | 1988-12-14 | 1990-06-15 | Delagrange Laboratoires | Application de benzamides substitues comme gastromoteurs |
| FR2640507A1 (fr) * | 1988-12-20 | 1990-06-22 | Delagrange Laboratoires | Application de benzamides substitues comme anxiolytiques et anti-psychotiques |
| FR2645742A1 (fr) * | 1989-04-12 | 1990-10-19 | Delagrange Laboratoires | Application de derives de 2-methoxy 4-(4,5-dihydro 2-imidazolyl (ou 2-oxazolyl) amino) 5-chloro benzamide dans le traitement des troubles de la fonction cognitive |
| US5401851A (en) * | 1992-06-03 | 1995-03-28 | Eli Lilly And Company | Angiotensin II antagonists |
| US20050140688A1 (en) * | 2003-12-29 | 2005-06-30 | Kim Pallister | Method and mechanism for programmable filtering of texture map data in 3D graphics subsystems |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3342826A (en) * | 1964-01-13 | 1967-09-19 | Ile De France | Heterocyclic aminoalkyl benzamides |
| FR1539104A (fr) * | 1967-07-31 | 1968-09-13 | Ile De France | Nouveaux benzamides et leur procédé de préparation |
| US3682968A (en) * | 1969-06-25 | 1972-08-08 | Merck & Co Inc | Anti-inflammatory salicylic acid derivatives |
| DE1963193A1 (de) * | 1969-12-17 | 1971-06-24 | Bayer Ag | N-substituierte 2-Arylimino-oxazolidine,Verfahren zu ihrer Herstellung und ihre Verwendung als Ektoparasiticide |
| FR2432513A1 (fr) * | 1977-10-24 | 1980-02-29 | Merieux Inst | Nouveaux derives de la thiazoline et leur application comme medicaments |
| DE2905883A1 (de) * | 1979-02-16 | 1980-08-28 | Boehringer Sohn Ingelheim | Radioimmuntest fuer clonidin |
| US4461904A (en) * | 1981-11-20 | 1984-07-24 | Alcon Laboratories, Inc. | 2-(Trisubstituted phenylimino)-imidazolines |
| CA1201066A (en) * | 1981-11-20 | 1986-02-25 | Alcon Laboratories, Inc. | N-¬3,5-dichloro-4-(2-imidazolidinylideneamino)- phenyl|-acetamide solutions for lowering intraocular pressure |
| DE3514351A1 (de) * | 1985-04-20 | 1986-11-06 | Boehringer Ingelheim KG, 6507 Ingelheim | Neue substituierte 2-(n-alkinyl-n-phenyl)amino)-imidazolinderivate, deren saeureadditionssalze, diese enthaltende arzneimittel und verfahren zu deren herstellung |
| JPS6341471A (ja) * | 1986-08-08 | 1988-02-22 | Nippon Soda Co Ltd | オキサ（チア）ゾリジン誘導体、その製造法及び殺ダニ剤 |
| US4826990A (en) * | 1987-09-30 | 1989-05-02 | American Home Products Corporation | 2-aryl substituted heterocyclic compounds as antiallergic and antiinflammatory agents |
-
1985
- 1985-12-19 FR FR8518829A patent/FR2592042B1/fr not_active Expired
-
1986
- 1986-12-15 AT AT86402796T patent/ATE57376T1/de active
- 1986-12-15 ES ES198686402796T patent/ES2036178T3/es not_active Expired - Lifetime
- 1986-12-15 EP EP86402796A patent/EP0236646B1/fr not_active Expired - Lifetime
- 1986-12-15 IE IE327086A patent/IE59212B1/en not_active IP Right Cessation
- 1986-12-15 DE DE8686402796T patent/DE3674916D1/de not_active Expired - Lifetime
- 1986-12-16 IN IN983/MAS/86A patent/IN163130B/en unknown
- 1986-12-16 CH CH4997/86A patent/CH671396A5/fr not_active IP Right Cessation
- 1986-12-17 DD DD86297795A patent/DD260495A5/de not_active IP Right Cessation
- 1986-12-17 NZ NZ218675A patent/NZ218675A/xx unknown
- 1986-12-17 MA MA21067A patent/MA20835A1/fr unknown
- 1986-12-17 AR AR86306202A patent/AR242193A1/es active
- 1986-12-17 DE DE19863643103 patent/DE3643103A1/de not_active Withdrawn
- 1986-12-17 PH PH34606A patent/PH24365A/en unknown
- 1986-12-17 IS IS3178A patent/IS1448B6/is unknown
- 1986-12-17 GB GB8630143A patent/GB2184723B/en not_active Expired
- 1986-12-17 HU HU865271A patent/HU196794B/hu not_active IP Right Cessation
- 1986-12-17 IL IL81010A patent/IL81010A/xx not_active IP Right Cessation
- 1986-12-18 YU YU2179/86A patent/YU44796B/xx unknown
- 1986-12-18 NO NO865148A patent/NO168176C/no unknown
- 1986-12-18 OA OA59022A patent/OA08564A/xx unknown
- 1986-12-18 AU AU66687/86A patent/AU586057B2/en not_active Ceased
- 1986-12-18 DK DK612886A patent/DK612886A/da not_active Application Discontinuation
- 1986-12-18 CN CN86108972A patent/CN1018454B/zh not_active Expired
- 1986-12-18 ZM ZM106/86A patent/ZM10686A1/xx unknown
- 1986-12-18 SU SU864028722A patent/SU1496632A3/ru active
- 1986-12-18 CA CA000525719A patent/CA1298301C/fr not_active Expired - Lifetime
- 1986-12-18 KR KR1019860010868A patent/KR930004653B1/ko not_active Expired - Fee Related
- 1986-12-18 PL PL1986263078A patent/PL148408B1/pl unknown
- 1986-12-18 FI FI865190A patent/FI865190A7/fi not_active Application Discontinuation
- 1986-12-19 JP JP61305136A patent/JPS62246553A/ja active Pending
- 1986-12-19 ZW ZW248/86A patent/ZW24886A1/xx unknown
- 1986-12-19 CS CS960386A patent/CS274285B2/cs unknown
- 1986-12-19 PT PT83982A patent/PT83982B/pt not_active IP Right Cessation
- 1986-12-19 US US06/943,708 patent/US4835172A/en not_active Expired - Fee Related
- 1986-12-19 ZA ZA869560A patent/ZA869560B/xx unknown
- 1986-12-19 TN TNTNSN86165A patent/TNSN86165A1/fr unknown
-
1988
- 1988-02-17 PH PH36522A patent/PH24469A/en unknown
-
1989
- 1989-03-13 US US07/322,122 patent/US4914117A/en not_active Expired - Fee Related
-
1990
- 1990-10-22 CA CA000615908A patent/CA1299579C/fr not_active Expired - Lifetime
- 1990-11-13 GR GR90400910T patent/GR3002524T3/el unknown
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