CH629198A5 - Procede de preparation de nouveaux 2,3-alkylene-bis (oxy)-benzamides substitues. - Google Patents
Procede de preparation de nouveaux 2,3-alkylene-bis (oxy)-benzamides substitues. Download PDFInfo
- Publication number
- CH629198A5 CH629198A5 CH956277A CH956277A CH629198A5 CH 629198 A5 CH629198 A5 CH 629198A5 CH 956277 A CH956277 A CH 956277A CH 956277 A CH956277 A CH 956277A CH 629198 A5 CH629198 A5 CH 629198A5
- Authority
- CH
- Switzerland
- Prior art keywords
- benzodioxane
- group
- substituted
- water
- carboxylic acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 19
- 238000002360 preparation method Methods 0.000 title claims description 7
- 229940054066 benzamide antipsychotics Drugs 0.000 title claims description 5
- -1 py-rimidinyl Chemical group 0.000 claims description 91
- 239000002253 acid Substances 0.000 claims description 46
- 150000001875 compounds Chemical class 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 125000003277 amino group Chemical group 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000006193 alkinyl group Chemical group 0.000 claims description 9
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- 125000003441 thioacyl group Chemical group 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 4
- 125000002541 furyl group Chemical group 0.000 claims 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims 2
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 claims 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 239000011574 phosphorus Substances 0.000 claims 1
- 238000005956 quaternization reaction Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 147
- 239000000243 solution Substances 0.000 description 118
- 239000000203 mixture Substances 0.000 description 111
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 109
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 90
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 77
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 74
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 57
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 52
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 51
- 238000003756 stirring Methods 0.000 description 50
- 239000013078 crystal Substances 0.000 description 47
- 239000002244 precipitate Substances 0.000 description 46
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 229960000583 acetic acid Drugs 0.000 description 30
- 235000011054 acetic acid Nutrition 0.000 description 29
- 239000002585 base Substances 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 229910021529 ammonia Inorganic materials 0.000 description 26
- 239000002904 solvent Substances 0.000 description 22
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 21
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- UNRBEYYLYRXYCG-UHFFFAOYSA-N (1-ethylpyrrolidin-2-yl)methanamine Chemical compound CCN1CCCC1CN UNRBEYYLYRXYCG-UHFFFAOYSA-N 0.000 description 18
- 239000006229 carbon black Substances 0.000 description 18
- 238000010992 reflux Methods 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- YVQZSNWNRKHUCY-UHFFFAOYSA-N 2H-1,5-benzodioxepine-6-carboxylic acid Chemical compound O1CC=COC2=C1C=CC=C2C(=O)O YVQZSNWNRKHUCY-UHFFFAOYSA-N 0.000 description 17
- 238000001816 cooling Methods 0.000 description 17
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 16
- 238000001953 recrystallisation Methods 0.000 description 16
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 15
- YCRGMNXARTVRLB-UHFFFAOYSA-N 2h-1,5-benzodioxepine Chemical compound O1C=CCOC2=CC=CC=C21 YCRGMNXARTVRLB-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- PTQOHBUFHOTLIZ-UHFFFAOYSA-N n-methyl-2,3-dihydro-1,4-benzodioxine-6-sulfonamide Chemical compound O1CCOC2=CC(S(=O)(=O)NC)=CC=C21 PTQOHBUFHOTLIZ-UHFFFAOYSA-N 0.000 description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
- 125000004442 acylamino group Chemical group 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 8
- VCLSWKVAHAJSFL-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=CC=C2C(=O)O VCLSWKVAHAJSFL-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
- 150000003857 carboxamides Chemical class 0.000 description 8
- 229910052736 halogen Inorganic materials 0.000 description 8
- 150000002367 halogens Chemical class 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- JUFKJRCMBLLXNH-UHFFFAOYSA-N (1-methylpyrrolidin-2-yl)methanamine Chemical compound CN1CCCC1CN JUFKJRCMBLLXNH-UHFFFAOYSA-N 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- NCSFGFOXYGSSSH-UHFFFAOYSA-N 7-chlorosulfonyl-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S(Cl)(=O)=O)C=C2C(=O)O NCSFGFOXYGSSSH-UHFFFAOYSA-N 0.000 description 7
- HTGKTSVPJJNEMQ-QMMMGPOBSA-N [(2s)-1-prop-2-enylpyrrolidin-2-yl]methanamine Chemical compound NC[C@@H]1CCCN1CC=C HTGKTSVPJJNEMQ-QMMMGPOBSA-N 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 238000010907 mechanical stirring Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 description 6
- RKSFKFSIQAQPHQ-UHFFFAOYSA-N 7-(methylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carbonyl chloride Chemical compound O1CCOC2=C1C=C(S(=O)(=O)NC)C=C2C(Cl)=O RKSFKFSIQAQPHQ-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- KHDSNFILCIVZDT-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-7-(methylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)NC)=CC2=C1OCCO2 KHDSNFILCIVZDT-UHFFFAOYSA-N 0.000 description 6
- YRXDDQLZROFCKK-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-7-ethylsulfonyl-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=CC2=C1OCCO2 YRXDDQLZROFCKK-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- OIYLTYTXMKZKCR-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound O1CCOC2=C1C=CC=C2C(=O)N OIYLTYTXMKZKCR-UHFFFAOYSA-N 0.000 description 5
- CPMCLKDETDGEHH-UHFFFAOYSA-N 2H-1,5-benzodioxepine-6-carboxamide Chemical compound O1CC=COC2=C1C=CC=C2C(=O)N CPMCLKDETDGEHH-UHFFFAOYSA-N 0.000 description 5
- LKYLYFSTNNVQNS-UHFFFAOYSA-N 5-amino-2,3-dihydro-1,4-benzodioxine-8-carboxylic acid Chemical compound O1CCOC2=C1C(C(O)=O)=CC=C2N LKYLYFSTNNVQNS-UHFFFAOYSA-N 0.000 description 5
- AVKRNLXCZBBZMD-UHFFFAOYSA-N 7-nitro-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C([N+]([O-])=O)C=C2C(=O)O AVKRNLXCZBBZMD-UHFFFAOYSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
- 229910006074 SO2NH2 Inorganic materials 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 230000002903 catalepsic effect Effects 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- POVZSJGKGZYZPS-UHFFFAOYSA-N n-[(1-methylpyrrolidin-2-yl)methyl]-7-(methylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound C=1C(S(=O)(=O)NC)=CC=2OCCOC=2C=1C(=O)NCC1CCCN1C POVZSJGKGZYZPS-UHFFFAOYSA-N 0.000 description 5
- 235000010288 sodium nitrite Nutrition 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- LYCFLVALOZTFDX-UHFFFAOYSA-N 5-acetamido-2,3-dihydro-1,4-benzodioxine-8-carboxylic acid Chemical compound O1CCOC2=C1C(C(O)=O)=CC=C2NC(=O)C LYCFLVALOZTFDX-UHFFFAOYSA-N 0.000 description 4
- PWJRPWPPVFPUQD-UHFFFAOYSA-N 5-methoxy-2,3-dihydro-1,4-benzodioxine-8-carboxylic acid Chemical compound O1CCOC2=C1C(C(O)=O)=CC=C2OC PWJRPWPPVFPUQD-UHFFFAOYSA-N 0.000 description 4
- MVYGNUFUGOZHQE-UHFFFAOYSA-N 66411-18-5 Chemical compound O1CCOC2=C1C([N+]([O-])=O)=C(Br)C(Br)=C2C(=O)O MVYGNUFUGOZHQE-UHFFFAOYSA-N 0.000 description 4
- ZRISRDUHJZSFSK-UHFFFAOYSA-N 7-(dimethylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S(=O)(=O)N(C)C)C=C2C(O)=O ZRISRDUHJZSFSK-UHFFFAOYSA-N 0.000 description 4
- NQEQVGJQJCYZNI-UHFFFAOYSA-N 7-(methylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S(=O)(=O)NC)C=C2C(O)=O NQEQVGJQJCYZNI-UHFFFAOYSA-N 0.000 description 4
- FSRYNXDRMYDGKD-UHFFFAOYSA-N 7-amino-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(N)C=C2C(O)=O FSRYNXDRMYDGKD-UHFFFAOYSA-N 0.000 description 4
- AJEDNQSLTXJFJG-UHFFFAOYSA-N 7-ethylsulfonyl-2,3-dihydro-1,4-benzodioxine-5-carbonyl chloride Chemical compound O1CCOC2=C1C=C(S(=O)(=O)CC)C=C2C(Cl)=O AJEDNQSLTXJFJG-UHFFFAOYSA-N 0.000 description 4
- ZHWMIKHMSOYRBC-UHFFFAOYSA-N 7-ethylsulfonyl-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S(=O)(=O)CC)C=C2C(O)=O ZHWMIKHMSOYRBC-UHFFFAOYSA-N 0.000 description 4
- GPKDBCCYRICYKP-UHFFFAOYSA-N 7-sulfamoyl-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S(=O)(=O)N)C=C2C(O)=O GPKDBCCYRICYKP-UHFFFAOYSA-N 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- SXAKAOFKGIOPHK-UHFFFAOYSA-N methyl 7-sulfamoyl-2,3-dihydro-1,4-benzodioxine-5-carboxylate Chemical compound O1CCOC2=C1C=C(S(N)(=O)=O)C=C2C(=O)OC SXAKAOFKGIOPHK-UHFFFAOYSA-N 0.000 description 4
- JYHVHIHNOSYGLA-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-5-methoxy-2,3-dihydro-1,4-benzodioxine-8-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC=C(OC)C2=C1OCCO2 JYHVHIHNOSYGLA-UHFFFAOYSA-N 0.000 description 4
- 229910017604 nitric acid Inorganic materials 0.000 description 4
- 231100000957 no side effect Toxicity 0.000 description 4
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical class ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
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- OAMPULWQGDEOHG-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-6-sulfonamide Chemical compound O1CCOC2=CC(S(=O)(=O)N)=CC=C21 OAMPULWQGDEOHG-UHFFFAOYSA-N 0.000 description 3
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- 230000001624 sedative effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000005049 silicon tetrachloride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D321/00—Heterocyclic compounds containing rings having two oxygen atoms as the only ring hetero atoms, not provided for by groups C07D317/00 - C07D319/00
- C07D321/02—Seven-membered rings
- C07D321/10—Seven-membered rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Reproductive Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Anesthesiology (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7623835A FR2360305A1 (fr) | 1976-08-04 | 1976-08-04 | Nouveaux 2,3-alkylene bis (oxy)benzamides substitues, leurs derives et leurs procedes de preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH629198A5 true CH629198A5 (fr) | 1982-04-15 |
Family
ID=9176558
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH956277A CH629198A5 (fr) | 1976-08-04 | 1977-08-03 | Procede de preparation de nouveaux 2,3-alkylene-bis (oxy)-benzamides substitues. |
Country Status (37)
| Country | Link |
|---|---|
| JP (1) | JPS57167914A (de) |
| AR (1) | AR219709A1 (de) |
| AT (1) | AT358034B (de) |
| AU (1) | AU516033B2 (de) |
| BE (1) | BE857350A (de) |
| BG (1) | BG36496A3 (de) |
| CA (1) | CA1114371A (de) |
| CH (1) | CH629198A5 (de) |
| CS (1) | CS216246B2 (de) |
| DD (1) | DD133237A5 (de) |
| DE (1) | DE2760414C2 (de) |
| DK (1) | DK152366C (de) |
| EG (1) | EG12716A (de) |
| ES (1) | ES461175A1 (de) |
| FI (1) | FI63938C (de) |
| GR (1) | GR61351B (de) |
| HK (2) | HK40382A (de) |
| HU (1) | HU179064B (de) |
| IE (2) | IE45646B1 (de) |
| IL (2) | IL52644A0 (de) |
| IN (1) | IN145473B (de) |
| LU (1) | LU77897A1 (de) |
| MC (1) | MC1154A1 (de) |
| MW (1) | MW2077A1 (de) |
| NL (1) | NL172063C (de) |
| NO (1) | NO152133C (de) |
| NZ (1) | NZ184816A (de) |
| OA (1) | OA05728A (de) |
| PH (3) | PH22114A (de) |
| PL (1) | PL111071B1 (de) |
| PT (1) | PT66865B (de) |
| RO (1) | RO72963A (de) |
| SE (2) | SE440776B (de) |
| SU (1) | SU716523A3 (de) |
| YU (1) | YU40005B (de) |
| ZA (1) | ZA774701B (de) |
| ZM (1) | ZM6077A1 (de) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9027098D0 (en) * | 1990-12-13 | 1991-02-06 | Beecham Group Plc | Pharmaceuticals |
| US10083697B2 (en) | 2015-05-27 | 2018-09-25 | Google Llc | Local persisting of data for selectively offline capable voice action in a voice-enabled electronic device |
| JP6452575B2 (ja) * | 2015-08-19 | 2019-01-16 | 株式会社トクヤマ | ミルタザピンの製造方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1473829A (fr) * | 1964-06-09 | 1967-03-24 | Ile De France | Nu-(tertiaire-aminoalkyl)-méthylène dioxybenzamides et leur préparation |
-
1977
- 1977-07-11 MC MC771250A patent/MC1154A1/xx unknown
- 1977-07-29 PT PT6686577A patent/PT66865B/pt unknown
- 1977-07-29 ES ES461175A patent/ES461175A1/es not_active Expired
- 1977-07-29 BG BG037047A patent/BG36496A3/xx unknown
- 1977-07-29 IN IN1165/CAL/77A patent/IN145473B/en unknown
- 1977-07-29 DE DE19772760414 patent/DE2760414C2/de not_active Expired - Fee Related
- 1977-07-29 GR GR54066A patent/GR61351B/el unknown
- 1977-08-01 YU YU188277A patent/YU40005B/xx unknown
- 1977-08-01 BE BE1008313A patent/BE857350A/xx not_active IP Right Cessation
- 1977-08-01 OA OA56243A patent/OA05728A/xx unknown
- 1977-08-01 AU AU27507/77A patent/AU516033B2/en not_active Expired
- 1977-08-02 RO RO9124577A patent/RO72963A/ro unknown
- 1977-08-02 EG EG45577A patent/EG12716A/xx active
- 1977-08-02 LU LU77897A patent/LU77897A1/xx unknown
- 1977-08-02 IE IE1600/77A patent/IE45646B1/en not_active IP Right Cessation
- 1977-08-02 AT AT569677A patent/AT358034B/de not_active IP Right Cessation
- 1977-08-02 IE IE2409/80A patent/IE45647B1/en not_active IP Right Cessation
- 1977-08-03 MW MW2077A patent/MW2077A1/xx unknown
- 1977-08-03 SE SE7708849A patent/SE440776B/xx not_active IP Right Cessation
- 1977-08-03 NO NO772739A patent/NO152133C/no unknown
- 1977-08-03 CH CH956277A patent/CH629198A5/fr not_active IP Right Cessation
- 1977-08-03 HU HUSO001195 patent/HU179064B/hu not_active IP Right Cessation
- 1977-08-03 DK DK346977A patent/DK152366C/da not_active IP Right Cessation
- 1977-08-03 IL IL52644A patent/IL52644A0/xx not_active IP Right Cessation
- 1977-08-03 DD DD20042077A patent/DD133237A5/de not_active IP Right Cessation
- 1977-08-03 ZA ZA00774701A patent/ZA774701B/xx unknown
- 1977-08-03 CA CA283,994A patent/CA1114371A/en not_active Expired
- 1977-08-03 NZ NZ18481677A patent/NZ184816A/xx unknown
- 1977-08-03 NL NL7708616A patent/NL172063C/xx not_active IP Right Cessation
- 1977-08-04 CS CS775179A patent/CS216246B2/cs unknown
- 1977-08-04 ZM ZM6077A patent/ZM6077A1/xx unknown
- 1977-08-04 PH PH20078A patent/PH22114A/en unknown
- 1977-08-04 FI FI772362A patent/FI63938C/fi not_active IP Right Cessation
- 1977-08-04 SU SU772507701A patent/SU716523A3/ru active
- 1977-08-04 PL PL1977200066A patent/PL111071B1/pl not_active IP Right Cessation
- 1977-08-08 AR AR26867377A patent/AR219709A1/es active
-
1981
- 1981-03-25 PH PH25426-AA patent/PH18629A/en unknown
- 1981-08-07 PH PH26025A patent/PH17710A/en unknown
-
1982
- 1982-03-19 JP JP4547682A patent/JPS57167914A/ja active Granted
- 1982-06-25 IL IL66138A patent/IL66138A0/xx not_active IP Right Cessation
- 1982-09-16 HK HK40382A patent/HK40382A/xx unknown
- 1982-09-16 HK HK40482A patent/HK40482A/xx unknown
- 1982-11-17 SE SE8206546A patent/SE453390B/sv not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |