CH641154A5 - Benzamides heterocycliques substitues. - Google Patents
Benzamides heterocycliques substitues. Download PDFInfo
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- CH641154A5 CH641154A5 CH289083A CH289083A CH641154A5 CH 641154 A5 CH641154 A5 CH 641154A5 CH 289083 A CH289083 A CH 289083A CH 289083 A CH289083 A CH 289083A CH 641154 A5 CH641154 A5 CH 641154A5
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- Prior art keywords
- formula
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- substituted heterocyclic
- methoxy
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- 229940054066 benzamide antipsychotics Drugs 0.000 title claims description 3
- 150000003936 benzamides Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 9
- -1 heterocyclic benzamides Chemical class 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 4
- QTWZISKLRIHFNO-UHFFFAOYSA-N n-(2,5-dichloropentyl)-2-methoxy-5-sulfamoylbenzamide Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1C(=O)NCC(Cl)CCCCl QTWZISKLRIHFNO-UHFFFAOYSA-N 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 150000001602 bicycloalkyls Chemical group 0.000 claims 1
- 238000009835 boiling Methods 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000013067 intermediate product Substances 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 229930195734 saturated hydrocarbon Natural products 0.000 claims 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- ATGSLQBVSZNJMT-UHFFFAOYSA-N 2,5-dichloropentan-1-amine;hydrochloride Chemical compound Cl.NCC(Cl)CCCCl ATGSLQBVSZNJMT-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- XFZMCFJADJFEBB-UHFFFAOYSA-N 2-methoxy-5-sulfamoylbenzoyl chloride Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1C(Cl)=O XFZMCFJADJFEBB-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- CFGDUGSIBUXRMR-UHFFFAOYSA-N 1,2-dihydropyrrol-2-ide Chemical compound C=1C=[C-]NC=1 CFGDUGSIBUXRMR-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OAMHTTBNEJBIKA-UHFFFAOYSA-N 2,2,2-trichloro-1-phenylethanone Chemical compound ClC(Cl)(Cl)C(=O)C1=CC=CC=C1 OAMHTTBNEJBIKA-UHFFFAOYSA-N 0.000 description 1
- SQAILWDRVDGLGY-UHFFFAOYSA-N 2-methoxy-5-sulfamoylbenzoic acid Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1C(O)=O SQAILWDRVDGLGY-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000006229 carbon black Substances 0.000 description 1
- 150000004651 carbonic acid esters Chemical class 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- HBGGXOJOCNVPFY-UHFFFAOYSA-N diisononyl phthalate Chemical compound CC(C)CCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCC(C)C HBGGXOJOCNVPFY-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- CPLWIGOCCLYPGK-UHFFFAOYSA-N n-[(1-cyclopropylpyrrolidin-2-yl)methyl]-2-methoxy-5-sulfamoylbenzamide Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1C(=O)NCC1N(C2CC2)CCC1 CPLWIGOCCLYPGK-UHFFFAOYSA-N 0.000 description 1
- YNOGYQAEJGADFJ-UHFFFAOYSA-N oxolan-2-ylmethanamine Chemical compound NCC1CCCO1 YNOGYQAEJGADFJ-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
-
- 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
-
- 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
- C07C65/28—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups having unsaturation outside the aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- 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
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- Neurology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
La présente invention a pour objet de nouveaux benzamides hétérocycliques substitués de formule V définis dans la revendication 1.
Les composés de la formule V selon l'invention peuvent être préparés par réaction d'un acide de formule:
COOK
ägent d1activstion dérivé réactif de l'acide
R,
R,
(II)
E2N-(CH2)n -y
(iv) Hai BaO
CONH •
ou l'un de ses dérivés réactifs tels qu'halogénure d'acide, ester d'alkyle, ester réactif comme ester méthoxyméthylique ou ester cya-nométhylique, ester aromatique, N-hydroximide-ester, anhydride symétrique ou anhydride mixte formé par exemple à partir d'un ester d'acide carbonique ou d'un ester haloformique, azide, hydrazide, azolide, isothiocyanate d'acide, trichloroacétophénone, dérivée de triphénylphosphine, avec une dihaloalkylamine de formule:
IÌ?K
(CK,) /. n
Hai
La réaction d'amidification peut être effectuée en présence ou en l'absence de solvant.
Les systèmes utilisés comme solvants, inertes vis-à-vis de la réaction d'amidification, sont par exemple des alcools, polyols, cétones, benzène, toluène, dioxanne, chloroforme, diméthyléther du diéthylè-neglycol. Il est aussi possible d'utiliser comme solvant un excès de l'amine employée comme matière première. Il peut être préférable de
Les composés de formule I ainsi que leurs sels d'addition avec des acides pharmacologiquement acceptables, leurs sels d'ammonium quaternaire, leurs oxydes et leurs isomères dextrogyres et lévo-
3
641154
gyres, ont d'intéressantes propriétés pharmacologiques et sont utiles notamment dans le domaine de la psychiatrie.
Dans l'exemple suivant, on décrit la préparation d'un composé préféré selon l'invention.
Exemple:
Chlorhydrate de 2,5-dichloropentylamine
Dans un ballon de 10 1 muni d'une agitation mécanique, d'un réfrigérant relié à un barboteur contenant de l'acide sulfurique et un tube d'arrivée de gaz, on introduit 1010 g (10 mol) de tétrahydrofur- 10 furylamine et on fait passer un courant d'acide chlorhydrique, préalablement séché par barbotage dans l'acide sulfurique, en maintenant la température à 100-110°C.
La réaction est exothermique au début. Lorsque le débit gazeux est identique à l'entrée et à la sortie, on retire le tube, on laisse re- 15 froidir vers 60° C, et on ajoute 41 de chloroforme, en agitant. On laisse la température baisser à 30° C, et on ajoute goutte à goutte 1500 ml de chlorure de thionyle. Après 2 h de reflux, le chlorhydrate de 2,5-dichloropentylamine précipite. On le filtre, on le lave au chloroforme, on le sèche à 70°C. On obtient 1512 g (rendement 78,5%) 20 de produit fondant à 160°C.
Chlorure de 2-mêthoxy-5-sulfamoylbenzoyle
Dans un ballon de 11 muni d'un agitateur mécanique, d'une ampoule à brome et d'un réfrigérant, on introduit 23,1 g (0,1 mol) 25 d'acide 2-méthoxy-5-sulfamoylbenzoïque dans 400 ml de dichlor-éthane et 1 ml de diméthylformamide. Sous agitation, on ajoute rapidement 11 ml (0,15 mol) de chlorure de thionyle, et on chauffe à reflux jusqu'à dissolution totale.
Après refroidissement à 50° C, on filtre et on sèche le chlorure 30 obtenu, dans un dessiccateur à vide.
On obtient 20,2 g de chlorure de 2-méthoxy-5-sulfamoylbenzoyle fondant à 167°C (avec décomposition).
Analyse pour Cl: Calculé:
Trouve:
N-( 2,5-dichloropenty l)-2-méthoxy-5-sulfamoylbenzamide
Dans un ballon de 21 muni d'un agitateur, d'un thermomètre, d'un réfrigérant et d'une ampoule à brome, on introduit 77,5 g (0,4 mol) de chlorhydrate de 2,5-dichloropentylamine dissous dans 500 ml de dichloréthane, puis 112 ml de triéthylamine. On coule alors, en maintenant la température à 20° C, une solution de 100 g (0,4 mol) de chlorure de 2-méthoxy-5-sulfamoylbenzoyle dans 11 de mé-thyléthylcétone.
Après 1 h de réaction, le précipité de chlorhydrate de triéthylamine est filtré, et le filtrat est évaporé à sec sous vide. Le précipité est dissous dans 11 d'eau. Il reste des cristaux qu'on filtre, et lave par 2 fois 100 ml d'isopropanol. On les ajoute au résidu du filtrat évaporé et on recristallise le solide dans 1600 ml d'isopropanol. On filtre, on lave à l'isopropanol, et on sèche à l'étuve à 40° C. On recueille, comme composé selon l'invention, 101 g (68,4%) de N-(2,5-dichloropentyl)-2-méthoxy-5-sulfamoylbenzamide fondant à 148° C.
Par rapport au schéma précédent, on peut continuer cette synthèse par exemple de la manière suivante.
Dans un flacon de 250 ml, on introduit 36,9 g (0,1 mol) du N-(2,5-dichloropentyl)-2-méthoxy-5-sulfamoylbenzamide obtenu et 57 g de cyclopropylamine. On porte 6 h à reflux, on laisse reposer 1 nuit, puis on reporte 5 h à reflux. La suspension obtenue est versée dans 300 ml d'eau et 50 g de glace. Le précipité blanc est lavé à l'eau, séché à l'étuve à 60°C. Il fond à 163°C et pèse 29,5 g (83,6%). On le dissout dans 2 1 d'acétonitrile et on filtre en présence de noir de carbone. On laisse cristalliser le filtrat.
On filtre, lave à l'acétonitrile et sèche à 40° C les cristaux obtenus. On recueille, comme composé de formule I, 67 g (rendement 74,9%) de N-(l-cyclopropyl-2-pyrrolidinylméthyl)-2-méthoxy-5-sulfamoylbenzamide, fondant à 180°C.
Analyse:
Calculé: N 11,89% S 9,07%
Trouvé: NI 1,74 S 9,19%
14,22% 14,6%
r
Claims (2)
- 6411542REVENDICATIONS 1. Benzamides hétérocycliques substitués de formule:cone (ce0) ^ n coirtî (ch.)■ - n chauffer le mélange réactionnel pendant l'amidification, par- exemple jusqu'au point d'ébullition des solvants cités ci-dessus.Les composés de formule V selon l'invention sont des produits intermédiaires utilisés dans la synthèse des nouveaux composés de s formule:(I)Rdans laquelle:— n est égal à 0,1, 2 ou 3,— R5 est un atome d'hydrogène, un groupe alkyle comportant 1 à 3 atomes de carbone, un groupe alcényle ou alcynyle,— Ri, R2, R3, R6 sont des atomes d'hydrogène ou d'halogène, des groupes alkyle, alcoxy, amino, acétamino, sulfamoyle, alkylsul-famoyle, dialkylsulfamoyle, alkylsulfonyle ou alkylsulfinyle, ou bien sont liés entre eux pour former un groupe azimido, et— Hai représente un atome de chlore, de brome ou d'iode.
- 2. Le N-(2,5-dichloropentyl)-2-méthoxy-5-sulfamoylbenzamide comme composé selon la revendication 1.dans laquelle:— R4 est un groupe cycloalkyle, cycloalcényle, bicycloalkyle ou 20 tricycloalkyle, et— A est une simple liaison ou une chaîne hydrocarbonée saturée ou insaturée comportant 1 à 3 atomes de carbone.Le procédé de préparation desdits composés de formule I se déroule par exemple selon le schéma suivant:25:ook do
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR7801633A FR2424909A1 (fr) | 1978-01-20 | 1978-01-20 | Nouveaux derives d'ortho-anisamides utiles comme medicaments modificateurs du comportement, et leurs procedes de preparation |
FR7831458A FR2440946A2 (fr) | 1978-01-20 | 1978-11-07 | Nouveaux benzamides heterocycliques substitues, leurs procedes de preparation et leur application comme modificateurs du comportement |
Publications (1)
Publication Number | Publication Date |
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CH641154A5 true CH641154A5 (fr) | 1984-02-15 |
Family
ID=26220412
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH50979A CH639369A5 (fr) | 1978-01-20 | 1979-01-18 | Benzamides heterocycliques substitues et leurs procedes de preparation. |
CH289083A CH641154A5 (fr) | 1978-01-20 | 1983-05-26 | Benzamides heterocycliques substitues. |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH50979A CH639369A5 (fr) | 1978-01-20 | 1979-01-18 | Benzamides heterocycliques substitues et leurs procedes de preparation. |
Country Status (39)
Country | Link |
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US (2) | US4673686A (fr) |
JP (1) | JPS54138553A (fr) |
AR (2) | AR221355A1 (fr) |
AT (2) | AT377254B (fr) |
AU (1) | AU520746B2 (fr) |
BE (1) | BE873522A (fr) |
BG (2) | BG48335A3 (fr) |
CA (1) | CA1133477A (fr) |
CH (2) | CH639369A5 (fr) |
CS (2) | CS241039B2 (fr) |
CY (1) | CY1202A (fr) |
DD (1) | DD141521A5 (fr) |
DE (1) | DE2901170A1 (fr) |
DK (1) | DK157008C (fr) |
EG (1) | EG13764A (fr) |
ES (2) | ES476757A1 (fr) |
FI (1) | FI69833C (fr) |
FR (1) | FR2440946A2 (fr) |
GB (2) | GB2083459B (fr) |
GR (1) | GR64398B (fr) |
HK (1) | HK12284A (fr) |
HU (1) | HU177902B (fr) |
IE (2) | IE48209B1 (fr) |
IL (2) | IL56413A (fr) |
IN (1) | IN150618B (fr) |
IT (1) | IT1164821B (fr) |
LU (1) | LU80793A1 (fr) |
MC (1) | MC1231A1 (fr) |
MX (2) | MX6192E (fr) |
NL (1) | NL7900455A (fr) |
NO (1) | NO153530C (fr) |
NZ (2) | NZ189381A (fr) |
OA (1) | OA06153A (fr) |
PL (1) | PL117195B1 (fr) |
PT (1) | PT69069A (fr) |
RO (2) | RO76554A (fr) |
SE (2) | SE449862B (fr) |
SU (1) | SU1158040A3 (fr) |
YU (2) | YU41608B (fr) |
Families Citing this family (18)
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SE8101536L (sv) * | 1981-03-11 | 1982-09-12 | Astra Laekemedel Ab | Bensamid-derivat |
SE8205135D0 (sv) * | 1982-09-09 | 1982-09-09 | Astra Laekemedel Ab | Benzamido-derivatives |
CH656126A5 (de) * | 1983-08-18 | 1986-06-13 | Ciba Geigy Ag | Durch 2-propynyloxygruppen substituierte phthalsaeureanhydride. |
SE8400478D0 (sv) * | 1984-01-31 | 1984-01-31 | Astra Laekemedel Ab | Oxysalicylamido derivatives |
US5240957A (en) * | 1984-01-31 | 1993-08-31 | Astra Lakemedel Akteibolag | Oxysalicylamido derivatives |
FR2574795B1 (fr) * | 1984-12-18 | 1987-11-20 | Ile De France | Nouveau procede industriel de synthese du n-((1'-allyl 2'-pyrrolidinyl) methyl) 2-methoxy 4,5-azimido benzamide |
FR2586018B1 (fr) * | 1985-08-12 | 1988-03-25 | Ile De France | Nouveau benzodioxepanne, son procede de synthese et ses applications en therapeutique |
US4772459A (en) * | 1986-09-09 | 1988-09-20 | Erbamont, Inc. | Method for controlling emesis caused by chemotherapeutic agents and antiemetic agents useful therein |
EP0320630A1 (fr) * | 1987-11-19 | 1989-06-21 | The Vanderbilt University | Iodobenzamides énantiomeriques |
US5154913A (en) * | 1987-11-19 | 1992-10-13 | Vanderbilt University | Radioiodinated benzamines method of their use as radioimaging agents |
CN1054980A (zh) * | 1990-02-19 | 1991-10-02 | 杏林制药株式会社 | 具有旋光活性的8-甲氧基喹诺酮羧酸衍生物,它们的制备方法以及它们的中间体 |
FR2678266A1 (fr) * | 1991-06-28 | 1992-12-31 | Delagrange Laboratoires | Nouveaux derives de 2-hydroxy 4-amino 5-ethylsulfonyl benzamide utiles comme anxiolytiques. |
US6517811B2 (en) | 1993-05-06 | 2003-02-11 | Research Corporation Technologies, Inc. | Compounds for cancer imaging and therapy |
US5911970A (en) * | 1993-05-06 | 1999-06-15 | Research Corporation Technologies, Inc. | Methods for cancer imaging and therapy using benzamine compounds |
US5993777A (en) * | 1993-05-06 | 1999-11-30 | Research Corporation Technologies, Inc. | Benzamide compounds for cancer imaging and therapy |
WO1994026314A1 (fr) * | 1993-05-06 | 1994-11-24 | John Christy S | Composes destines a la visualisation et a la therapie du cancer |
CN103450058B (zh) * | 2013-09-18 | 2015-10-14 | 广安凯特医药化工有限公司 | 一种氨磺必利酸的制备方法 |
CN105503666A (zh) * | 2015-12-30 | 2016-04-20 | 苏州诚和医药化学有限公司 | 一种便捷合成2-甲氧基-5-氨磺酰基苯甲酸甲酯的方法 |
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US3342826A (en) * | 1964-01-13 | 1967-09-19 | Ile De France | Heterocyclic aminoalkyl benzamides |
FR6787M (fr) * | 1967-08-17 | 1969-03-17 | ||
US3891671A (en) * | 1968-08-01 | 1975-06-24 | Ile De France | N-(2-pyrrolidyl or piperidyl alkyl)-4-hydroxy benzamides |
US3959477A (en) * | 1968-08-01 | 1976-05-25 | Societe D'etudes Scientifiques Et Industrielles De L'ile-De-France | Methods of protection against emesis in mammals by administration of a heterocyclic benzamide |
GB1364231A (en) * | 1968-12-23 | 1974-08-21 | Robins Co Inc A H | N-/1-substituted-3-pyrrolidinyl/benzamides and thiobenzamides |
US3577440A (en) * | 1968-12-23 | 1971-05-04 | Robins Co Inc A H | 1-substituted-3-amido-pyrrolidines |
FR2097031A1 (en) * | 1970-07-29 | 1972-03-03 | Berri Balzac | 2-aminoethoxyethyl-6,6-dimethyl nor pinane derivs - local anaesthetics spasmolytics and anticholinergics |
GB1392194A (en) * | 1971-09-23 | 1975-04-30 | Wyeth John & Brother Ltd | Pyrrolidine derivatives |
US3966957A (en) * | 1972-04-03 | 1976-06-29 | A. H. Robins Company, Incorporated | Method for controlling emesis with N-(1-substituted-3-pyrrolidinyl)benzamides and thiobenzamides |
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US3862139A (en) * | 1972-06-23 | 1975-01-21 | Delmar Chem | Heterocyclic benzamide compounds |
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CH605793A5 (fr) * | 1974-03-05 | 1978-10-13 | Ile De France | |
US4158060A (en) * | 1974-12-18 | 1979-06-12 | Synthelabo | 2-Methoxy-benzamide derivatives |
DE2556457C3 (de) * | 1974-12-18 | 1981-02-12 | Synthelabo S.A., Paris | N-(Pyrrolidin-2-yl-methyl)-2-methoxybenzamide, deren Salze, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
US4172143A (en) * | 1974-12-18 | 1979-10-23 | Synthelabo | 2-Methoxy-benzamide derivatives |
US4039672A (en) * | 1975-01-11 | 1977-08-02 | Societe D'etudes Scientifiques Et Industrielles De L'ile-De-France | N-(1'-allypyrrolidinyl 2'-methyl) 2-methoxy 4,5-azimido benzamide and its pharmaceutically acceptable salts |
GB1520584A (en) * | 1975-04-02 | 1978-08-09 | Yamanouchi Pharma Co Ltd | 2 - alkoxy - 5 substituted benzamide derivatives and their use in pharmaceutical compositions |
US4197243A (en) * | 1975-04-02 | 1980-04-08 | Yamanouchi Pharmaceutical Co., Ltd. | N-1-Benzyl-3-pyrrolidinyl-4-dimethylamino benzamide derivatives |
CH614709A5 (fr) * | 1975-09-25 | 1979-12-14 | Ciba Geigy Ag | |
JPS5248661A (en) * | 1975-10-14 | 1977-04-18 | Synthelabo | 22methoxyybenzamide derivatives |
NZ186175A (en) * | 1977-01-27 | 1980-03-05 | Shionogi & Co | Meta-sulphonamidobenzamide derivatives |
FR2415099A1 (fr) * | 1978-01-20 | 1979-08-17 | Ile De France | Nouveaux derives de 4-amino-5-alkylsulfonyl ortho-anisamides, leurs procedes de preparation et leur application comme psychotropes |
US4350691A (en) * | 1979-12-20 | 1982-09-21 | Beecham Group Limited | Certain azabicyclocarboxamides and compositions containing same |
IL61972A0 (en) * | 1980-01-30 | 1981-02-27 | Beecham Group Ltd | Azabicyclic compounds,their preparation and pharmaceutical compositions containing them |
US4352802A (en) * | 1980-06-10 | 1982-10-05 | Beecham Group Limited | Bicyclo[3.3.1]nonyl-benzamide |
FR2493848B2 (fr) * | 1980-11-07 | 1986-05-16 | Delalande Sa | Nouveaux derives des nor-tropane et granatane, leur procede de preparation et leur application en therapeutique |
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1978
- 1978-11-07 FR FR7831458A patent/FR2440946A2/fr active Granted
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1979
- 1979-01-11 MC MC791354A patent/MC1231A1/fr unknown
- 1979-01-11 AR AR275135A patent/AR221355A1/es active
- 1979-01-11 ES ES476757A patent/ES476757A1/es not_active Expired
- 1979-01-11 IL IL56413A patent/IL56413A/xx unknown
- 1979-01-12 PT PT69069A patent/PT69069A/fr unknown
- 1979-01-13 DE DE19792901170 patent/DE2901170A1/de active Granted
- 1979-01-15 AU AU43374/79A patent/AU520746B2/en not_active Ceased
- 1979-01-15 NZ NZ189381A patent/NZ189381A/en unknown
- 1979-01-15 BG BG042076A patent/BG48335A3/xx unknown
- 1979-01-15 BG BG043504A patent/BG48336A3/xx unknown
- 1979-01-15 GR GR58091A patent/GR64398B/el unknown
- 1979-01-16 LU LU80793A patent/LU80793A1/fr unknown
- 1979-01-17 CY CY1202A patent/CY1202A/xx unknown
- 1979-01-17 SE SE7900419A patent/SE449862B/sv not_active IP Right Cessation
- 1979-01-17 GB GB8119940A patent/GB2083459B/en not_active Expired
- 1979-01-17 BE BE1/9242A patent/BE873522A/fr not_active IP Right Cessation
- 1979-01-17 EG EG28/79A patent/EG13764A/xx active
- 1979-01-17 GB GB7901688A patent/GB2013662B/en not_active Expired
- 1979-01-17 IN IN46/CAL/79A patent/IN150618B/en unknown
- 1979-01-17 YU YU105/79A patent/YU41608B/xx unknown
- 1979-01-18 CH CH50979A patent/CH639369A5/fr not_active IP Right Cessation
- 1979-01-18 DK DK021079A patent/DK157008C/da not_active IP Right Cessation
- 1979-01-18 IT IT47707/79A patent/IT1164821B/it active
- 1979-01-18 RO RO7996327A patent/RO76554A/fr unknown
- 1979-01-18 NO NO790179A patent/NO153530C/no unknown
- 1979-01-18 RO RO79103351A patent/RO80716A/fr unknown
- 1979-01-19 OA OA56713A patent/OA06153A/fr unknown
- 1979-01-19 CS CS8380A patent/CS241039B2/cs unknown
- 1979-01-19 DD DD79210558A patent/DD141521A5/de unknown
- 1979-01-19 FI FI790181A patent/FI69833C/fi not_active IP Right Cessation
- 1979-01-19 HU HU79SO1242A patent/HU177902B/hu not_active IP Right Cessation
- 1979-01-19 MX MX797670U patent/MX6192E/es unknown
- 1979-01-19 AT AT0039779A patent/AT377254B/de not_active IP Right Cessation
- 1979-01-19 NL NL7900455A patent/NL7900455A/xx not_active Application Discontinuation
- 1979-01-19 CS CS79444A patent/CS241016B2/cs unknown
- 1979-01-19 JP JP548479A patent/JPS54138553A/ja active Granted
- 1979-01-19 PL PL1979212898A patent/PL117195B1/pl unknown
- 1979-01-19 CA CA319,968A patent/CA1133477A/fr not_active Expired
- 1979-01-19 MX MX7911207U patent/MX7622E/es unknown
- 1979-01-19 SU SU792712702A patent/SU1158040A3/ru active
- 1979-01-30 IE IE2021/81A patent/IE48209B1/en not_active IP Right Cessation
- 1979-01-30 IE IE91/79A patent/IE48208B1/en not_active IP Right Cessation
- 1979-02-16 ES ES477783A patent/ES477783A1/es not_active Expired
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1980
- 1980-07-10 AR AR281712A patent/AR221428A1/es active
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1981
- 1981-03-04 NZ NZ196409A patent/NZ196409A/xx unknown
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1982
- 1982-02-03 IL IL64928A patent/IL64928A0/xx not_active IP Right Cessation
- 1982-12-03 YU YU2685/82A patent/YU43809B/xx unknown
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1983
- 1983-05-26 CH CH289083A patent/CH641154A5/fr not_active IP Right Cessation
- 1983-08-24 AT AT0301483A patent/AT377979B/de not_active IP Right Cessation
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1984
- 1984-02-16 HK HK122/84A patent/HK12284A/xx unknown
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1985
- 1985-08-26 US US06/769,796 patent/US4673686A/en not_active Expired - Fee Related
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1986
- 1986-04-30 US US06/858,906 patent/US4816471A/en not_active Expired - Fee Related
- 1986-10-16 SE SE8604394A patent/SE463972B/sv not_active IP Right Cessation
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