DD260065A5 - Verfahren zur herstellung von dihydrobenzofuran- und chroman-carboxamid-derivaten - Google Patents

Verfahren zur herstellung von dihydrobenzofuran- und chroman-carboxamid-derivaten Download PDF

Info

Publication number: DD260065A5
Authority: DD; German Democratic Republic
Prior art keywords: group; temperature; formula; methyl; water
Prior art date: 1986-01-30

Application number

DD87299591A

Other languages

German (de)

English (en)

Inventor

Jacqueline Franceschini

Josette Margarit

Original Assignee

��@��k��

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1986-01-30

Filing date

1987-01-29

Publication date

1988-09-14

1987-01-29 Application filed by ��@��k�� filed Critical ��@��k��

1988-09-14 Publication of DD260065A5 publication Critical patent/DD260065A5/de

Links

HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 title abstract description 9
229940053202 antiepileptics carboxamide derivative Drugs 0.000 title abstract 2
VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 title abstract 2
238000004519 manufacturing process Methods 0.000 title 1
239000002253 acid Substances 0.000 claims abstract description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 15
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
229910052801 chlorine Inorganic materials 0.000 claims abstract description 8
125000000217 alkyl group Chemical group 0.000 claims abstract description 7
230000003287 optical effect Effects 0.000 claims abstract description 6
125000003277 amino group Chemical group 0.000 claims abstract description 5
239000001257 hydrogen Substances 0.000 claims abstract description 5
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
150000003839 salts Chemical class 0.000 claims abstract description 4
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 30
238000000034 method Methods 0.000 claims description 12
238000002360 preparation method Methods 0.000 claims description 8
150000001412 amines Chemical class 0.000 claims description 7
125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
125000005843 halogen group Chemical group 0.000 claims description 4
AFYJYAWBTFNDAN-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-2-carboxamide Chemical class C1=CC=C2OC(C(=O)N)CCC2=C1 AFYJYAWBTFNDAN-UHFFFAOYSA-N 0.000 claims description 3
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
241000251730 Chondrichthyes Species 0.000 claims 4
150000007513 acids Chemical class 0.000 claims 1
125000003342 alkenyl group Chemical group 0.000 claims 1
230000015572 biosynthetic process Effects 0.000 claims 1
238000003786 synthesis reaction Methods 0.000 claims 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 152
239000000243 solution Substances 0.000 description 146
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 131
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 84
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 80
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 79
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 69
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 62
KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 62
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 56
239000000203 mixture Substances 0.000 description 56
239000000047 product Substances 0.000 description 56
238000001816 cooling Methods 0.000 description 45
239000013078 crystal Substances 0.000 description 41
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 38
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 34
239000002244 precipitate Substances 0.000 description 33
229910021529 ammonia Inorganic materials 0.000 description 31
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
-1 Alkenyi group Chemical group 0.000 description 30
239000003610 charcoal Substances 0.000 description 27
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 22
235000011121 sodium hydroxide Nutrition 0.000 description 21
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 19
229910000027 potassium carbonate Inorganic materials 0.000 description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 16
230000007704 transition Effects 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
238000009835 boiling Methods 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 14
IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 14
238000010992 reflux Methods 0.000 description 14
238000003756 stirring Methods 0.000 description 13
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
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 12
229960004046 apomorphine Drugs 0.000 description 12
239000007789 gas Substances 0.000 description 12
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
241000700159 Rattus Species 0.000 description 9
238000001035 drying Methods 0.000 description 9
238000012360 testing method Methods 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
229910000041 hydrogen chloride Inorganic materials 0.000 description 8
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 7
241000699666 Mus <mouse, genus> Species 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
238000004090 dissolution Methods 0.000 description 6
239000001530 fumaric acid Substances 0.000 description 6
238000010438 heat treatment Methods 0.000 description 6
230000000144 pharmacologic effect Effects 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
238000007920 subcutaneous administration Methods 0.000 description 6
UNRBEYYLYRXYCG-UHFFFAOYSA-N (1-ethylpyrrolidin-2-yl)methanamine Chemical compound CCN1CCCC1CN UNRBEYYLYRXYCG-UHFFFAOYSA-N 0.000 description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
229940025084 amphetamine Drugs 0.000 description 5
230000008485 antagonism Effects 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000010410 layer Substances 0.000 description 5
239000007787 solid Substances 0.000 description 5
XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 5
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
208000009132 Catalepsy Diseases 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
206010047853 Waxy flexibility Diseases 0.000 description 4
238000007912 intraperitoneal administration Methods 0.000 description 4
CEQFOVLGLXCDCX-WUKNDPDISA-N methyl red Chemical compound C1=CC(N(C)C)=CC=C1\N=N\C1=CC=CC=C1C(O)=O CEQFOVLGLXCDCX-WUKNDPDISA-N 0.000 description 4
230000004899 motility Effects 0.000 description 4
230000002269 spontaneous effect Effects 0.000 description 4
239000000725 suspension Substances 0.000 description 4
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
ZHKWLZDQDAJMDE-UHFFFAOYSA-N 4-amino-5-chloro-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=C(N)C2=C1OC(C)C2 ZHKWLZDQDAJMDE-UHFFFAOYSA-N 0.000 description 3
YIYMIUAFLOAZGG-UHFFFAOYSA-N 5-chloro-n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound C=12OC(C)CC2=CC(Cl)=CC=1C(=O)NCC1CCCN1CC1=CCCCC1 YIYMIUAFLOAZGG-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 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
238000010521 absorption reaction Methods 0.000 description 3
230000001476 alcoholic effect Effects 0.000 description 3
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
230000006399 behavior Effects 0.000 description 3
VJGNLOIQCWLBJR-UHFFFAOYSA-M benzyl(tributyl)azanium;chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 VJGNLOIQCWLBJR-UHFFFAOYSA-M 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
239000005457 ice water Substances 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
XFOSLLKUFTXGDS-UHFFFAOYSA-N n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-6-(methylsulfamoyl)-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=1C(S(=O)(=O)NC)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1=CCCCC1 XFOSLLKUFTXGDS-UHFFFAOYSA-N 0.000 description 3
UHXBMSNEECJPSX-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1OCC2 UHXBMSNEECJPSX-UHFFFAOYSA-N 0.000 description 2
GGSGUFURNLIODZ-UHFFFAOYSA-N 2-methyl-5-(methylsulfamoyl)-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC(S(=O)(=O)NC)=CC2=C1OC(C)C2 GGSGUFURNLIODZ-UHFFFAOYSA-N 0.000 description 2
JVYRMZXDRCKMNK-UHFFFAOYSA-N 2-methyl-5-sulfanyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound SC1=CC(C(O)=O)=C2OC(C)CC2=C1 JVYRMZXDRCKMNK-UHFFFAOYSA-N 0.000 description 2
IKLTWEQRKUTUMF-UHFFFAOYSA-N 5-chloro-n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound C=1C(Cl)=CC=2CCOC=2C=1C(=O)NCC1CCCN1CC1=CCCCC1 IKLTWEQRKUTUMF-UHFFFAOYSA-N 0.000 description 2
XBRJTRHVGGRYID-UHFFFAOYSA-N 6-chloro-n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=1C(Cl)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1=CCCCC1 XBRJTRHVGGRYID-UHFFFAOYSA-N 0.000 description 2
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
239000004342 Benzoyl peroxide Substances 0.000 description 2
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
206010042008 Stereotypy Diseases 0.000 description 2
QFIYFROFRTUSPW-UHFFFAOYSA-N [1-(cyclopropylmethyl)pyrrolidin-2-yl]methanamine Chemical compound NCC1CCCN1CC1CC1 QFIYFROFRTUSPW-UHFFFAOYSA-N 0.000 description 2
238000007112 amidation reaction Methods 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
229940101006 anhydrous sodium sulfite Drugs 0.000 description 2
230000003474 anti-emetic effect Effects 0.000 description 2
239000002111 antiemetic agent Substances 0.000 description 2
235000019400 benzoyl peroxide Nutrition 0.000 description 2
239000001569 carbon dioxide Substances 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
230000001484 cataleptigenic effect Effects 0.000 description 2
239000010949 copper Substances 0.000 description 2
ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
DSGUSEBCDAKBCM-UHFFFAOYSA-N ethane-1,2-disulfonic acid;dihydrate Chemical compound O.O.OS(=O)(=O)CCS(O)(=O)=O DSGUSEBCDAKBCM-UHFFFAOYSA-N 0.000 description 2
229910000042 hydrogen bromide Inorganic materials 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
DIXLBCFAIGTQNW-UHFFFAOYSA-N n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=1C(S(=O)(=O)CC)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1=CCCCC1 DIXLBCFAIGTQNW-UHFFFAOYSA-N 0.000 description 2
ROLSLQXAZBRPOA-UHFFFAOYSA-N n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=1C(S(=O)(=O)CC)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1CC1 ROLSLQXAZBRPOA-UHFFFAOYSA-N 0.000 description 2
230000000701 neuroleptic effect Effects 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
229940001584 sodium metabisulfite Drugs 0.000 description 2
235000010262 sodium metabisulphite Nutrition 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
229940001482 sodium sulfite Drugs 0.000 description 2
235000010265 sodium sulphite Nutrition 0.000 description 2
239000000126 substance Substances 0.000 description 2
238000012546 transfer Methods 0.000 description 2
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
ATGSLQBVSZNJMT-UHFFFAOYSA-N 2,5-dichloropentan-1-amine;hydrochloride Chemical compound Cl.NCC(Cl)CCCCl ATGSLQBVSZNJMT-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
HBRCDTRQDHMTDA-UHFFFAOYSA-N 2-[[4-(diethylamino)phenyl]diazenyl]benzoic acid Chemical compound C1=CC(N(CC)CC)=CC=C1N=NC1=CC=CC=C1C(O)=O HBRCDTRQDHMTDA-UHFFFAOYSA-N 0.000 description 1
ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
229940093475 2-ethoxyethanol Drugs 0.000 description 1
HWCCVMGTQFWJSS-UHFFFAOYSA-N 2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound C1=CC(C(O)=O)=C2OC(C)CC2=C1 HWCCVMGTQFWJSS-UHFFFAOYSA-N 0.000 description 1
LOFOWPRKKPHPDW-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C=CC=C2C(=O)O LOFOWPRKKPHPDW-UHFFFAOYSA-N 0.000 description 1
DVURTEWCGPFUBO-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C2=C1OC(C)C2 DVURTEWCGPFUBO-UHFFFAOYSA-N 0.000 description 1
QVCKVMSEINXIDN-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-n,2-dimethyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound CCN(CC)CCN(C)C(=O)C1=CC(Cl)=C(N)C2=C1OC(C)C2 QVCKVMSEINXIDN-UHFFFAOYSA-N 0.000 description 1
FYAKLZKQJDBBKW-UHFFFAOYSA-N 4-bromo-2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1O FYAKLZKQJDBBKW-UHFFFAOYSA-N 0.000 description 1
KPRWPAVXFHNNHY-UHFFFAOYSA-N 5-(cyclopropylmethylsulfanyl)-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound C=1C(C(O)=O)=C2OC(C)CC2=CC=1SCC1CC1 KPRWPAVXFHNNHY-UHFFFAOYSA-N 0.000 description 1
WCLWARCNRCZCLX-UHFFFAOYSA-N 5-(cyclopropylmethylsulfonyl)-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound C=1C(C(O)=O)=C2OC(C)CC2=CC=1S(=O)(=O)CC1CC1 WCLWARCNRCZCLX-UHFFFAOYSA-N 0.000 description 1
ZTGYYMNIVDBVRY-UHFFFAOYSA-N 5-(cyclopropylmethylsulfonyl)-n-[(1-ethylpyrrolidin-2-yl)methyl]-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC2CC2)=CC2=C1OC(C)C2 ZTGYYMNIVDBVRY-UHFFFAOYSA-N 0.000 description 1
UCWRUKVGDLBXAB-UHFFFAOYSA-N 5-amino-n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-(methylsulfamoyl)-3,4-dihydro-2h-chromene-8-carboxamide;hydrochloride Chemical compound Cl.C=12OCCCC2=C(N)C(S(=O)(=O)NC)=CC=1C(=O)NCC1CCCN1CC1CC1 UCWRUKVGDLBXAB-UHFFFAOYSA-N 0.000 description 1
HMAQONNHUBCKQM-UHFFFAOYSA-N 5-amino-n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=12OCCCC2=C(N)C(S(=O)(=O)CC)=CC=1C(=O)NCC1CCCN1CC1CC1 HMAQONNHUBCKQM-UHFFFAOYSA-N 0.000 description 1
VTWDFRYGJWVOCB-UHFFFAOYSA-N 5-bromo-6-chlorosulfonyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C(Br)=C(S(Cl)(=O)=O)C=C2C(=O)O VTWDFRYGJWVOCB-UHFFFAOYSA-N 0.000 description 1
JKNYUUWDTUMXKG-UHFFFAOYSA-N 5-chlorosulfonyl-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound ClS(=O)(=O)C1=CC(C(O)=O)=C2OC(C)CC2=C1 JKNYUUWDTUMXKG-UHFFFAOYSA-N 0.000 description 1
IJMZGXWLELXQOL-UHFFFAOYSA-N 5-chlorosulfonyl-4-methoxy-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound C1=C(S(Cl)(=O)=O)C(OC)=C2CC(C)OC2=C1C(O)=O IJMZGXWLELXQOL-UHFFFAOYSA-N 0.000 description 1
YAUJLIGIQRIQFA-UHFFFAOYSA-N 5-cyclopropyl-2-methyl-2-methylsulfonyl-3H-1-benzofuran-7-carboxylic acid Chemical compound C1(CC1)C=1C=C(C2=C(CC(O2)(C)S(=O)(=O)C)C=1)C(=O)O YAUJLIGIQRIQFA-UHFFFAOYSA-N 0.000 description 1
BPKFAPZPAZSNPV-UHFFFAOYSA-N 5-ethylsulfonyl-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC(S(=O)(=O)CC)=CC2=C1OC(C)C2 BPKFAPZPAZSNPV-UHFFFAOYSA-N 0.000 description 1
NBFBKENIEVTKNL-UHFFFAOYSA-N 5-ethylsulfonyl-4-methoxy-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound CCS(=O)(=O)C1=CC(C(O)=O)=C2OC(C)CC2=C1OC NBFBKENIEVTKNL-UHFFFAOYSA-N 0.000 description 1
AFOVEAQMIPOAHV-UHFFFAOYSA-N 5-methyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound O1CCCC2=C1C(C(O)=O)=CC=C2C AFOVEAQMIPOAHV-UHFFFAOYSA-N 0.000 description 1
FIZZPCFLWSCSPU-UHFFFAOYSA-N 6-(cyclopropylmethyl)-3,4-dihydro-2h-chromene-8-carbothioic s-acid Chemical compound C=1C=2CCCOC=2C(C(=S)O)=CC=1CC1CC1 FIZZPCFLWSCSPU-UHFFFAOYSA-N 0.000 description 1
WFQGBZVMZKKVIY-UHFFFAOYSA-N 6-chlorosulfonyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C=C(S(Cl)(=O)=O)C=C2C(=O)O WFQGBZVMZKKVIY-UHFFFAOYSA-N 0.000 description 1
GIBFKPSXYYCRPS-UHFFFAOYSA-N 6-sulfanyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C=C(S)C=C2C(=O)O GIBFKPSXYYCRPS-UHFFFAOYSA-N 0.000 description 1
IOXHMEKPPVJDDG-UHFFFAOYSA-N C1CC(=S(=O)=O)OC2=C1C=CC=C2C(=O)O Chemical compound C1CC(=S(=O)=O)OC2=C1C=CC=C2C(=O)O IOXHMEKPPVJDDG-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
206010022998 Irritability Diseases 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
230000007059 acute toxicity Effects 0.000 description 1
231100000403 acute toxicity Toxicity 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
230000000561 anti-psychotic effect Effects 0.000 description 1
229940125683 antiemetic agent Drugs 0.000 description 1
239000003699 antiulcer agent Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
230000003542 behavioural effect Effects 0.000 description 1
ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
230000002903 catalepsic effect Effects 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
150000001907 coumarones Chemical class 0.000 description 1
AYQJCDBGGILQIZ-UHFFFAOYSA-N cyclohexen-1-ylmethanamine Chemical compound NCC1=CCCCC1 AYQJCDBGGILQIZ-UHFFFAOYSA-N 0.000 description 1
WRPMREPGSFVNAQ-UHFFFAOYSA-N cyclopropylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CC1 WRPMREPGSFVNAQ-UHFFFAOYSA-N 0.000 description 1
238000001514 detection method Methods 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
125000006125 ethylsulfonyl group Chemical group 0.000 description 1
230000005284 excitation Effects 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000011010 flushing procedure Methods 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
150000002431 hydrogen Chemical group 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000011835 investigation Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
230000002045 lasting effect Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
UITFCFWKYAOJEJ-UHFFFAOYSA-N methyl 2-hydroxy-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C=C1O UITFCFWKYAOJEJ-UHFFFAOYSA-N 0.000 description 1
LCXHOHRQXZMSQN-UHFFFAOYSA-N methyl 4-acetamido-2-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(NC(C)=O)C=C1O LCXHOHRQXZMSQN-UHFFFAOYSA-N 0.000 description 1
YBTQUOABZWFEGO-UHFFFAOYSA-N methyl 4-methyl-2-prop-2-enoxybenzoate Chemical compound COC(=O)C1=CC=C(C)C=C1OCC=C YBTQUOABZWFEGO-UHFFFAOYSA-N 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 1
GJZAXHCGEJGCKG-UHFFFAOYSA-N n-(2,5-dichloropentyl)-6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C1CCOC2=C1C=C(S(=O)(=O)CC)C=C2C(=O)NCC(Cl)CCCCl GJZAXHCGEJGCKG-UHFFFAOYSA-N 0.000 description 1
XRSGROYAHHYBQX-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC=CC2=C1OCCC2 XRSGROYAHHYBQX-UHFFFAOYSA-N 0.000 description 1
SEGNASMWALWFFW-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethylsulfonyl-4-methoxy-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=C(OC)C2=C1OC(C)C2 SEGNASMWALWFFW-UHFFFAOYSA-N 0.000 description 1
QUGQJQKLRQWWRD-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethylsulfonyl-4-methoxy-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide;hydrochloride Chemical compound Cl.CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=C(OC)C2=C1OC(C)C2 QUGQJQKLRQWWRD-UHFFFAOYSA-N 0.000 description 1
XGXIYBAHFAGGRU-UHFFFAOYSA-N n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-2-methyl-5-(methylsulfamoyl)-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound C=1C(S(=O)(=O)NC)=CC=2CC(C)OC=2C=1C(=O)NCC1CCCN1CC1=CCCCC1 XGXIYBAHFAGGRU-UHFFFAOYSA-N 0.000 description 1
DGXRDXCERKHGHV-UHFFFAOYSA-N n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-5-(cyclopropylmethylsulfonyl)-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound C=12OC(C)CC2=CC(S(=O)(=O)CC2CC2)=CC=1C(=O)NCC1CCCN1CC1=CCCCC1 DGXRDXCERKHGHV-UHFFFAOYSA-N 0.000 description 1
VOOZZNJPDWKHMO-UHFFFAOYSA-N n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-5-(cyclopropylmethylsulfonyl)-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.C=12OC(C)CC2=CC(S(=O)(=O)CC2CC2)=CC=1C(=O)NCC1CCCN1CC1=CCCCC1 VOOZZNJPDWKHMO-UHFFFAOYSA-N 0.000 description 1
KNOHDWRTKYWTFB-UHFFFAOYSA-N n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-5-ethylsulfonyl-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound C=1C(S(=O)(=O)CC)=CC=2CC(C)OC=2C=1C(=O)NCC1CCCN1CC1CC1 KNOHDWRTKYWTFB-UHFFFAOYSA-N 0.000 description 1
FMLJYMXKZJHZIN-UHFFFAOYSA-N n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-5-ethylsulfonyl-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide;hydrochloride Chemical compound Cl.C=1C(S(=O)(=O)CC)=CC=2CC(C)OC=2C=1C(=O)NCC1CCCN1CC1CC1 FMLJYMXKZJHZIN-UHFFFAOYSA-N 0.000 description 1
STOOEPYBPULNTR-UHFFFAOYSA-N n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-(cyclopropylmethylsulfonyl)-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=1C(S(=O)(=O)CC2CC2)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1CC1 STOOEPYBPULNTR-UHFFFAOYSA-N 0.000 description 1
DLIFJJJTIASJQU-UHFFFAOYSA-N n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxamide;hydrochloride Chemical compound Cl.C=1C(S(=O)(=O)CC)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1CC1 DLIFJJJTIASJQU-UHFFFAOYSA-N 0.000 description 1
IQNCFOOPRZLWKT-UHFFFAOYSA-N n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-ethylsulfonyl-5-methyl-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=12OCCCC2=C(C)C(S(=O)(=O)CC)=CC=1C(=O)NCC1CCCN1CC1CC1 IQNCFOOPRZLWKT-UHFFFAOYSA-N 0.000 description 1
239000003176 neuroleptic agent Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
QQOXBFUTRLDXDP-UHFFFAOYSA-N p-Aminosalicylic acid methyl ester Chemical compound COC(=O)C1=CC=C(N)C=C1O QQOXBFUTRLDXDP-UHFFFAOYSA-N 0.000 description 1
235000011837 pasties Nutrition 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
238000010298 pulverizing process Methods 0.000 description 1
VMPYTOIPVPQDNX-UHFFFAOYSA-N pyrrolidin-1-ylmethanamine Chemical compound NCN1CCCC1 VMPYTOIPVPQDNX-UHFFFAOYSA-N 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000027 toxicology Toxicity 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Neurology (AREA)
Neurosurgery (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)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Biomedical Technology (AREA)
Public Health (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrane Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicinal Preparation (AREA)
Hydrogenated Pyridines (AREA)
Furan Compounds (AREA)
Peptides Or Proteins (AREA)
Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Polyamides (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

DD87299591A 1986-01-30 1987-01-29 Verfahren zur herstellung von dihydrobenzofuran- und chroman-carboxamid-derivaten DD260065A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
FR8601279A FR2593504B1 (fr)	1986-01-30	1986-01-30	Nouveaux derives de dihydrobenzofuranne - et de chromane - carboxamides, leurs procedes de preparation et leur utilisation comme neuroleptiques

Publications (1)

Publication Number	Publication Date
DD260065A5 true DD260065A5 (de)	1988-09-14

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Application Number	Title	Priority Date	Filing Date
DD87299591A DD260065A5 (de)	1986-01-30	1987-01-29	Verfahren zur herstellung von dihydrobenzofuran- und chroman-carboxamid-derivaten

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US (1)	US5006570A (xx)
EP (1)	EP0231139B1 (xx)
JP (1)	JPS62277376A (xx)
KR (1)	KR870007160A (xx)
CN (2)	CN1016420B (xx)
AT (1)	ATE70063T1 (xx)
AU (1)	AU593605B2 (xx)
BE (1)	BE1000164A5 (xx)
BG (1)	BG46600A3 (xx)
CA (1)	CA1300161C (xx)
CH (1)	CH670827A5 (xx)
CS (2)	CS264288B2 (xx)
DD (1)	DD260065A5 (xx)
DE (2)	DE3702005A1 (xx)
DK (1)	DK46987A (xx)
ES (2)	ES2003671A6 (xx)
FI (1)	FI870347A (xx)
FR (1)	FR2593504B1 (xx)
GB (1)	GB2187188B (xx)
GR (2)	GR870134B (xx)
HU (1)	HU206107B (xx)
IE (1)	IE870128L (xx)
IL (1)	IL81299A (xx)
IN (2)	IN164389B (xx)
IS (1)	IS1446B6 (xx)
IT (1)	IT1205729B (xx)
LU (1)	LU86747A1 (xx)
MA (1)	MA20861A1 (xx)
NO (1)	NO168582C (xx)
NZ (1)	NZ219068A (xx)
OA (1)	OA08472A (xx)
PH (1)	PH23392A (xx)
PL (2)	PL152491B1 (xx)
PT (1)	PT84224B (xx)
SU (2)	SU1609451A3 (xx)
TN (1)	TNSN87012A1 (xx)
YU (1)	YU46185B (xx)
ZA (1)	ZA87552B (xx)
ZM (1)	ZM987A1 (xx)
ZW (1)	ZW1387A1 (xx)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2611713B1 (fr) *	1987-02-27	1990-11-30	Adir	Nouveaux derives de l'acide (dihydro-2,3 oxo-2 benzofurannyl-3)-2 acetique, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent
FR2611715B1 (fr) *	1987-02-27	1989-05-12	Adir	Nouveaux acetamides derives de la dihydro-2,3 phenyl-3 benzofurannone-2, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent
US5374637A (en) *	1989-03-22	1994-12-20	Janssen Pharmaceutica N.V.	N-(3-hydroxy-4-piperidinyl)(dihydrobenzofuran, dihydro-2H-benzopyran or dihydrobenzodioxin)carboxamide derivatives
JP2726306B2 (ja) *	1989-04-14	1998-03-11	本田技研工業株式会社	車両の前後輪操舵装置
US5122361A (en) *	1989-04-17	1992-06-16	Trustees Of The University Of Pennsylvania	Dopamine receptor ligands and imaging agents
EP0412939A3 (en) *	1989-08-11	1991-09-04	Ciba-Geigy Ag	Certain benzopyran and benzothiopyran derivatives
US5420151A (en) *	1989-12-22	1995-05-30	Aktiebolaget Astra	Chroman derivatives
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1986
- 1986-01-30 FR FR8601279A patent/FR2593504B1/fr not_active Expired
1987
- 1987-01-16 NO NO870199A patent/NO168582C/no unknown
- 1987-01-19 IL IL81299A patent/IL81299A/xx not_active IP Right Cessation
- 1987-01-20 IE IE870128A patent/IE870128L/xx unknown
- 1987-01-21 IN IN43/MAS/87A patent/IN164389B/en unknown
- 1987-01-21 IS IS3189A patent/IS1446B6/is unknown
- 1987-01-21 AU AU67855/87A patent/AU593605B2/en not_active Ceased
- 1987-01-23 DE DE19873702005 patent/DE3702005A1/de not_active Withdrawn
- 1987-01-23 ZW ZW13/87A patent/ZW1387A1/xx unknown
- 1987-01-26 ZA ZA87552A patent/ZA87552B/xx unknown
- 1987-01-27 NZ NZ219068A patent/NZ219068A/en unknown
- 1987-01-27 GR GR870134A patent/GR870134B/el unknown
- 1987-01-27 FI FI870347A patent/FI870347A/fi not_active Application Discontinuation
- 1987-01-27 MA MA21095A patent/MA20861A1/fr unknown
- 1987-01-27 YU YU11387A patent/YU46185B/sh unknown
- 1987-01-28 GB GB8701870A patent/GB2187188B/en not_active Expired
- 1987-01-28 CN CN87100978A patent/CN1016420B/zh not_active Expired
- 1987-01-28 TN TNTNSN87012A patent/TNSN87012A1/fr unknown
- 1987-01-28 BG BG078228A patent/BG46600A3/xx active Active
- 1987-01-28 LU LU86747A patent/LU86747A1/fr unknown
- 1987-01-28 CA CA000528418A patent/CA1300161C/fr not_active Expired - Lifetime
- 1987-01-28 KR KR870000673A patent/KR870007160A/ko not_active Application Discontinuation
- 1987-01-29 CH CH300/87A patent/CH670827A5/fr not_active IP Right Cessation
- 1987-01-29 ES ES8700216A patent/ES2003671A6/es not_active Expired
- 1987-01-29 DK DK046987A patent/DK46987A/da unknown
- 1987-01-29 PT PT84224A patent/PT84224B/pt not_active IP Right Cessation
- 1987-01-29 CS CS87578A patent/CS264288B2/cs unknown
- 1987-01-29 AT AT87400194T patent/ATE70063T1/de not_active IP Right Cessation
- 1987-01-29 EP EP87400194A patent/EP0231139B1/fr not_active Expired - Lifetime
- 1987-01-29 PH PH34786A patent/PH23392A/en unknown
- 1987-01-29 SU SU874028919A patent/SU1609451A3/ru active
- 1987-01-29 DE DE8787400194T patent/DE3774888D1/de not_active Expired - Lifetime
- 1987-01-29 DD DD87299591A patent/DD260065A5/de unknown
- 1987-01-29 IT IT47583/87A patent/IT1205729B/it active
- 1987-01-29 HU HU87283A patent/HU206107B/hu not_active IP Right Cessation
- 1987-01-29 ZM ZM9/87A patent/ZM987A1/xx unknown
- 1987-01-29 ES ES198787400194T patent/ES2038679T3/es not_active Expired - Lifetime
- 1987-01-29 OA OA59056A patent/OA08472A/xx unknown
- 1987-01-30 US US07/008,916 patent/US5006570A/en not_active Expired - Fee Related
- 1987-01-30 JP JP62021649A patent/JPS62277376A/ja active Pending
- 1987-01-30 PL PL1987272298A patent/PL152491B1/pl unknown
- 1987-01-30 BE BE8700065A patent/BE1000164A5/fr not_active Expired
- 1987-01-30 PL PL1987263885A patent/PL152404B1/pl unknown
1988
- 1988-01-19 CS CS88362A patent/CS264300B2/cs unknown
- 1988-05-23 IN IN343/MAS/88A patent/IN167060B/en unknown
- 1988-06-28 SU SU884355973A patent/SU1607688A3/ru active
1992
- 1992-01-04 CN CN92100139A patent/CN1062144A/zh active Pending
- 1992-01-27 GR GR920400082T patent/GR3003653T3/el unknown

Also Published As

Publication number	Publication date
GR870134B (en)	1987-05-28
CH670827A5 (xx)	1989-07-14
SU1609451A3 (ru)	1990-11-23
GB2187188A (en)	1987-09-03
PT84224A (fr)	1987-02-01
CS264288B2 (en)	1989-06-13
ZW1387A1 (en)	1987-10-28
EP0231139B1 (fr)	1991-12-04
IT1205729B (it)	1989-03-31
KR870007160A (ko)	1987-08-17
DE3774888D1 (de)	1992-01-16
BG46600A3 (en)	1990-01-15
ZM987A1 (en)	1987-09-30
HUT47093A (en)	1989-01-30
EP0231139A2 (fr)	1987-08-05
EP0231139A3 (en)	1988-04-27
ATE70063T1 (de)	1991-12-15
CA1300161C (fr)	1992-05-05
HU206107B (en)	1992-08-28
ES2003671A6 (es)	1988-11-01
DK46987D0 (da)	1987-01-29
FR2593504B1 (fr)	1988-12-09
FI870347A (fi)	1987-07-31
CS57887A2 (en)	1988-09-16
MA20861A1 (fr)	1987-10-01
IN164389B (xx)	1989-03-04
NZ219068A (en)	1990-12-21
PL263885A1 (en)	1988-09-15
CN1016420B (zh)	1992-04-29
CN87100978A (zh)	1987-09-16
IT8747583A0 (it)	1987-01-29
US5006570A (en)	1991-04-09
PT84224B (pt)	1989-03-30
IS1446B6 (is)	1990-12-14
IE870128L (en)	1987-07-30
DK46987A (da)	1987-07-31
TNSN87012A1 (fr)	1990-01-01
YU11387A (en)	1988-06-30
LU86747A1 (fr)	1987-06-02
NO168582C (no)	1992-03-11
GB2187188B (en)	1989-11-08
NO168582B (no)	1991-12-02
ZA87552B (en)	1987-10-28
AU593605B2 (en)	1990-02-15
FI870347A0 (fi)	1987-01-27
DE3702005A1 (de)	1987-08-06
CS264300B2 (cs)	1989-06-13
PL152404B1 (en)	1990-12-31
PH23392A (en)	1989-07-26
IS3189A7 (is)	1987-07-31
SU1607688A3 (ru)	1990-11-15
BE1000164A5 (fr)	1988-07-05
PL272298A1 (en)	1989-02-20
PL152491B1 (en)	1990-12-31
YU46185B (sh)	1993-05-28
GR3003653T3 (xx)	1993-03-16
CS36288A2 (en)	1988-09-16
IL81299A (en)	1991-09-16
IN167060B (xx)	1990-08-25
NO870199D0 (no)	1987-01-16
CN1062144A (zh)	1992-06-24
NO870199L (no)	1987-07-31
AU6785587A (en)	1987-08-06
OA08472A (fr)	1988-07-29
ES2038679T3 (es)	1993-08-01
FR2593504A1 (fr)	1987-07-31
JPS62277376A (ja)	1987-12-02
IL81299A0 (en)	1987-08-31
GB8701870D0 (en)	1987-03-04

Publication	Publication Date	Title
DD260065A5 (de)	1988-09-14	Verfahren zur herstellung von dihydrobenzofuran- und chroman-carboxamid-derivaten
DD300432A5 (de)	1992-06-11	Heterozyklische diaryletherverbindungen
DD202152A5 (de)	1983-08-31	Verfahren zur herstellung von phenylpiperazinderivaten
DE69329894T2 (de)	2001-05-03	Arylamidderivate
DE2925945A1 (de)	1980-01-10	Acylderivate von carnitin, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische mittel
DE60128112T2 (de)	2007-12-27	Aminoalkoxybenzoyl-benzofurane oder benzothiophene, verfahren zu ihrer herstellung und die enthaltenden zusammensetzungen
DE3830060A1 (de)	1990-03-15	2-phenylbenzimidazole - verfahren zu ihrer herstellung sowie diese verbindungen enthaltende arzneimittel
DE69708130T2 (de)	2002-06-20	A-oxo-butansäuren enthaltende pharmazeutische zusammensetzung
EP0071935A2 (de)	1983-02-16	1-Phenyl-2-aminocarbonylindol-Verbindungen sowie Verfahren und Zwischenprodukte zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
DE3211934A1 (de)	1983-10-13	Salicylsaeurederivate, verfahren zu ihrer herstellung, pharmazeutische praeparate auf basis dieser verbindungen und ihre verwendung
DE3326164A1 (de)	1985-01-31	Neue p-oxibenzoesaeure-derivate, sowie verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
DE2517020C3 (de)	1978-03-16	N- [l-(3-Trifluormethyl-phenyl)-prop-2-yl] -glycinester, Verfahren zu ihrer' Herstellung und diese Ester enthaltende Arzneimittel
DE4135473A1 (de)	1993-04-29	Triazaspirodecanon-methylchromane
DE68902946T2 (de)	1993-04-29	Heteroarotinoid-derivate, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammenstellungen.
DE3209304C2 (xx)	1988-03-31
AT391316B (de)	1990-09-25	Neue thienyloxy-alkylamin-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DD297402A5 (de)	1992-01-09	Neue aminopropanol-derivate, diese verbindungen als wirkstoff enthaltende arzneimittelpraeparate sowie verfahren zur herstellung derselben
DE2412520A1 (de)	1974-10-10	Tricyclische verbindungen
DE69107274T2 (de)	1995-07-13	Phenoxyessigsäure-Derivate, Verfahren zu ihrer Herstellung, und pharmazeutische Zusammensetzungen die sie enthalten.
DE1948507C2 (de)	1982-10-21	4-(2-Hydroxy-3-aminopropoxy)-indolderivate, ihre Salze, Verfahren zu ihrer Herstellung und Heilmittel
EP1148879A2 (de)	2001-10-31	Verwendung von pyrazol-carbonsäureamiden
DE3718765C2 (xx)	1989-08-03
DE2362877A1 (de)	1974-06-20	5,8-dihydro-5,8-methanonaphthaline mit kardiovaskulaerer wirkung
DD250533A5 (de)	1987-10-14	Verfahren zur herstellung eines dihydropyridinderivates
CH638490A5 (de)	1983-09-30	Anilide mit hustenhemmender wirkung und verfahren zur herstellung derselben.