NO322205B1 - Tricykliske forbindelser, deres fremstilling og anvendelse samt preparater inneholdende forbindelsene - Google Patents
Tricykliske forbindelser, deres fremstilling og anvendelse samt preparater inneholdende forbindelsene Download PDFInfo
- Publication number
- NO322205B1 NO322205B1 NO19983970A NO983970A NO322205B1 NO 322205 B1 NO322205 B1 NO 322205B1 NO 19983970 A NO19983970 A NO 19983970A NO 983970 A NO983970 A NO 983970A NO 322205 B1 NO322205 B1 NO 322205B1
- Authority
- NO
- Norway
- Prior art keywords
- compound
- group
- reaction
- acid
- compound according
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 487
- 238000002360 preparation method Methods 0.000 title claims description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 48
- 125000001424 substituent group Chemical group 0.000 claims abstract description 38
- 125000005843 halogen group Chemical group 0.000 claims abstract description 30
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 25
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 19
- 125000003277 amino group Chemical group 0.000 claims abstract description 18
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 claims abstract description 18
- 125000000623 heterocyclic group Chemical class 0.000 claims abstract description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 7
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
- -1 cyano, hydroxy Chemical group 0.000 claims description 158
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 112
- 238000000034 method Methods 0.000 claims description 109
- 239000003795 chemical substances by application Substances 0.000 claims description 41
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
- 230000009467 reduction Effects 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 22
- 238000007363 ring formation reaction Methods 0.000 claims description 15
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 14
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims description 14
- 229960003987 melatonin Drugs 0.000 claims description 13
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 12
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 8
- 102000001419 Melatonin receptor Human genes 0.000 claims description 8
- 108050009605 Melatonin receptor Proteins 0.000 claims description 8
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 230000001105 regulatory effect Effects 0.000 claims description 6
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 6
- 230000029936 alkylation Effects 0.000 claims description 5
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- 230000027455 binding Effects 0.000 claims description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 3
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
- 230000008454 sleep-wake cycle Effects 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 230000009471 action Effects 0.000 claims description 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 2
- 230000027288 circadian rhythm Effects 0.000 claims description 2
- 230000006806 disease prevention Effects 0.000 claims description 2
- 235000019256 formaldehyde Nutrition 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- SDSGISCYQWUIMI-UHFFFAOYSA-N n-[2-(2,6,7,8-tetrahydro-1h-cyclopenta[e][1]benzofuran-8-yl)ethyl]acetamide Chemical group C1=C2OCCC2=C2C(CCNC(=O)C)CCC2=C1 SDSGISCYQWUIMI-UHFFFAOYSA-N 0.000 claims description 2
- FCRJFCVXPXEUPT-UHFFFAOYSA-N n-[2-(7-phenyl-2,6-dihydro-1h-cyclopenta[e][1]benzofuran-8-yl)ethyl]propanamide Chemical compound C1C2=CC=C3OCCC3=C2C(CCNC(=O)CC)=C1C1=CC=CC=C1 FCRJFCVXPXEUPT-UHFFFAOYSA-N 0.000 claims description 2
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 125000000213 sulfino group Chemical group [H]OS(*)=O 0.000 claims description 2
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- RYYNBBSULBXPJL-BJMVGYQFSA-N (2e)-2-(1,2,6,7-tetrahydrocyclopenta[e][1]benzofuran-8-ylidene)ethanamine Chemical group C1=C2OCCC2=C2C(=C/CN)/CCC2=C1 RYYNBBSULBXPJL-BJMVGYQFSA-N 0.000 claims 1
- BFNUHWYOQCGTCA-UHFFFAOYSA-N 2-(2,6,7,8-tetrahydro-1h-cyclopenta[e][1]benzofuran-8-yl)ethanamine Chemical group C1=C2OCCC2=C2C(CCN)CCC2=C1 BFNUHWYOQCGTCA-UHFFFAOYSA-N 0.000 claims 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 1
- 150000002430 hydrocarbons Chemical class 0.000 abstract description 64
- 229930195733 hydrocarbon Natural products 0.000 abstract description 60
- 239000004215 Carbon black (E152) Substances 0.000 abstract description 8
- 125000001183 hydrocarbyl group Chemical group 0.000 abstract 2
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 356
- 239000002904 solvent Substances 0.000 description 244
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 186
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 186
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 171
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 159
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 149
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 134
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 116
- 239000011541 reaction mixture Substances 0.000 description 108
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 93
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 90
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 88
- 239000000203 mixture Substances 0.000 description 88
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 87
- 239000002585 base Substances 0.000 description 87
- 150000001408 amides Chemical class 0.000 description 85
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 82
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 82
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 78
- 230000035484 reaction time Effects 0.000 description 70
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 69
- 150000002170 ethers Chemical class 0.000 description 63
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 61
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 60
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 59
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 58
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 58
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 58
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 56
- 238000004587 chromatography analysis Methods 0.000 description 56
- 238000004821 distillation Methods 0.000 description 56
- 238000001953 recrystallisation Methods 0.000 description 56
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 52
- 150000001298 alcohols Chemical class 0.000 description 50
- 229910052751 metal Inorganic materials 0.000 description 50
- 239000002184 metal Substances 0.000 description 50
- 239000000047 product Substances 0.000 description 50
- 239000012043 crude product Substances 0.000 description 48
- 238000000926 separation method Methods 0.000 description 47
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 46
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 46
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 45
- 239000002253 acid Substances 0.000 description 45
- 150000003462 sulfoxides Chemical class 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 43
- 150000008282 halocarbons Chemical class 0.000 description 43
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 43
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 42
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 42
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 41
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 40
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 40
- 239000003054 catalyst Substances 0.000 description 39
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- 150000002148 esters Chemical group 0.000 description 31
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 30
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 30
- 229910000027 potassium carbonate Inorganic materials 0.000 description 29
- 229910000029 sodium carbonate Inorganic materials 0.000 description 29
- 239000000126 substance Substances 0.000 description 29
- 229940093915 gynecological organic acid Drugs 0.000 description 28
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 28
- 150000007524 organic acids Chemical class 0.000 description 28
- 235000005985 organic acids Nutrition 0.000 description 28
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 27
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 27
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 26
- 230000002378 acidificating effect Effects 0.000 description 26
- 150000004703 alkoxides Chemical class 0.000 description 26
- 150000002825 nitriles Chemical class 0.000 description 26
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 26
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 26
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 24
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 23
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 22
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 22
- 150000008046 alkali metal hydrides Chemical class 0.000 description 22
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 22
- 150000007529 inorganic bases Chemical class 0.000 description 22
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 22
- 229910000105 potassium hydride Inorganic materials 0.000 description 22
- 238000006722 reduction reaction Methods 0.000 description 22
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 22
- 239000012312 sodium hydride Substances 0.000 description 22
- 229910000104 sodium hydride Inorganic materials 0.000 description 22
- 239000002841 Lewis acid Substances 0.000 description 21
- SVYKKECYCPFKGB-UHFFFAOYSA-N N,N-dimethylcyclohexylamine Chemical compound CN(C)C1CCCCC1 SVYKKECYCPFKGB-UHFFFAOYSA-N 0.000 description 21
- 150000001447 alkali salts Chemical class 0.000 description 21
- 150000004982 aromatic amines Chemical class 0.000 description 21
- 238000007796 conventional method Methods 0.000 description 21
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 21
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 21
- 150000007517 lewis acids Chemical class 0.000 description 21
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 21
- 150000003512 tertiary amines Chemical class 0.000 description 21
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 21
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 21
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 20
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 18
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 18
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 18
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 18
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 18
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 18
- 238000006798 ring closing metathesis reaction Methods 0.000 description 18
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 18
- 239000002168 alkylating agent Substances 0.000 description 17
- 229910052987 metal hydride Inorganic materials 0.000 description 17
- 150000004681 metal hydrides Chemical class 0.000 description 17
- 229940100198 alkylating agent Drugs 0.000 description 16
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 16
- 229910000024 caesium carbonate Inorganic materials 0.000 description 16
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 16
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 15
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 15
- 230000002140 halogenating effect Effects 0.000 description 15
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 14
- 235000019253 formic acid Nutrition 0.000 description 14
- 229930195734 saturated hydrocarbon Natural products 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 13
- 229910017052 cobalt Inorganic materials 0.000 description 13
- 239000010941 cobalt Substances 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 12
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 239000007868 Raney catalyst Substances 0.000 description 12
- 229910000564 Raney nickel Inorganic materials 0.000 description 12
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 12
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 150000002576 ketones Chemical class 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 10
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 10
- 150000007513 acids Chemical class 0.000 description 10
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 10
- 150000004820 halides Chemical class 0.000 description 10
- 230000026030 halogenation Effects 0.000 description 10
- 238000005658 halogenation reaction Methods 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 150000007522 mineralic acids Chemical class 0.000 description 10
- 229910017604 nitric acid Inorganic materials 0.000 description 10
- 235000006408 oxalic acid Nutrition 0.000 description 10
- 229910052707 ruthenium Inorganic materials 0.000 description 10
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 9
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 9
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 9
- 239000000654 additive Substances 0.000 description 9
- 238000009835 boiling Methods 0.000 description 9
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 9
- 239000003638 chemical reducing agent Substances 0.000 description 9
- 239000001530 fumaric acid Substances 0.000 description 9
- 229940098779 methanesulfonic acid Drugs 0.000 description 9
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 9
- 239000011975 tartaric acid Substances 0.000 description 9
- 235000002906 tartaric acid Nutrition 0.000 description 9
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 229910052500 inorganic mineral Inorganic materials 0.000 description 8
- 235000010755 mineral Nutrition 0.000 description 8
- 239000011707 mineral Substances 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 8
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 8
- 239000007818 Grignard reagent Substances 0.000 description 7
- 150000008065 acid anhydrides Chemical class 0.000 description 7
- 239000003377 acid catalyst Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000010531 catalytic reduction reaction Methods 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 150000004795 grignard reagents Chemical class 0.000 description 7
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 7
- 239000011976 maleic acid Substances 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 6
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 229910015900 BF3 Inorganic materials 0.000 description 6
- 230000010933 acylation Effects 0.000 description 6
- 238000005917 acylation reaction Methods 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 6
- 238000005984 hydrogenation reaction Methods 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 150000007530 organic bases Chemical class 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 6
- 229910052723 transition metal Inorganic materials 0.000 description 6
- 150000003624 transition metals Chemical class 0.000 description 6
- 125000003282 alkyl amino group Chemical group 0.000 description 5
- 150000001350 alkyl halides Chemical class 0.000 description 5
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- 150000003003 phosphines Chemical class 0.000 description 5
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 5
- 229940080818 propionamide Drugs 0.000 description 5
- 150000003871 sulfonates Chemical class 0.000 description 5
- XDJWZONZDVNKDU-UHFFFAOYSA-N 1314-24-5 Chemical compound O=POP=O XDJWZONZDVNKDU-UHFFFAOYSA-N 0.000 description 4
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 4
- 101100020289 Xenopus laevis koza gene Proteins 0.000 description 4
- 238000005903 acid hydrolysis reaction Methods 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 4
- 229910001863 barium hydroxide Inorganic materials 0.000 description 4
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 4
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
- 229910052796 boron Inorganic materials 0.000 description 4
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 4
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 4
- 230000003301 hydrolyzing effect Effects 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- VSAISIQCTGDGPU-UHFFFAOYSA-N phosphorus trioxide Inorganic materials O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 description 4
- 229920000137 polyphosphoric acid Polymers 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 4
- 239000011592 zinc chloride Substances 0.000 description 4
- 235000005074 zinc chloride Nutrition 0.000 description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 3
- CFGDUGSIBUXRMR-UHFFFAOYSA-N 1,2-dihydropyrrol-2-ide Chemical class C=1C=[C-]NC=1 CFGDUGSIBUXRMR-UHFFFAOYSA-N 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 3
- UYGLXGHUDBKZKX-UHFFFAOYSA-N 2-(chloromethyl)pyridin-1-ium;iodide Chemical compound [I-].ClCC1=CC=CC=[NH+]1 UYGLXGHUDBKZKX-UHFFFAOYSA-N 0.000 description 3
- DSXKRMRFCSAUNO-UHFFFAOYSA-M 2-fluoro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1F DSXKRMRFCSAUNO-UHFFFAOYSA-M 0.000 description 3
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- TZCYLJGNWDVJRA-UHFFFAOYSA-N 6-chloro-1-hydroxybenzotriazole Chemical compound C1=C(Cl)C=C2N(O)N=NC2=C1 TZCYLJGNWDVJRA-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 3
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 3
- 229910002651 NO3 Inorganic materials 0.000 description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 3
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- 150000004075 acetic anhydrides Chemical class 0.000 description 3
- 239000002535 acidifier Substances 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 125000004103 aminoalkyl group Chemical group 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 150000001540 azides Chemical class 0.000 description 3
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 3
- 239000012964 benzotriazole Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 150000001649 bromium compounds Chemical class 0.000 description 3
- LKXYJYDRLBPHRS-UHFFFAOYSA-N bromocyclopropane Chemical compound BrC1CC1 LKXYJYDRLBPHRS-UHFFFAOYSA-N 0.000 description 3
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical class CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 150000001805 chlorine compounds Chemical class 0.000 description 3
- JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N hydrogen peroxide Substances OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 3
- 238000006317 isomerization reaction Methods 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- 229910052759 nickel Inorganic materials 0.000 description 3
- 238000006396 nitration reaction Methods 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 3
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
- 239000003444 phase transfer catalyst Substances 0.000 description 3
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 3
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 3
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 229910003446 platinum oxide Inorganic materials 0.000 description 3
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 3
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical class CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 3
- 229910052703 rhodium Inorganic materials 0.000 description 3
- 239000010948 rhodium Substances 0.000 description 3
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 3
- 238000007086 side reaction Methods 0.000 description 3
- 150000007970 thio esters Chemical class 0.000 description 3
- 150000005206 1,2-dihydroxybenzenes Chemical class 0.000 description 2
- OGFAWKRXZLGJSK-UHFFFAOYSA-N 1-(2,4-dihydroxyphenyl)-2-(4-nitrophenyl)ethanone Chemical compound OC1=CC(O)=CC=C1C(=O)CC1=CC=C([N+]([O-])=O)C=C1 OGFAWKRXZLGJSK-UHFFFAOYSA-N 0.000 description 2
- SNUSZUYTMHKCPM-UHFFFAOYSA-N 1-hydroxypyridin-2-one Chemical compound ON1C=CC=CC1=O SNUSZUYTMHKCPM-UHFFFAOYSA-N 0.000 description 2
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- KWMBADTWRIGGGG-UHFFFAOYSA-N 2-diethoxyphosphorylacetonitrile Chemical compound CCOP(=O)(CC#N)OCC KWMBADTWRIGGGG-UHFFFAOYSA-N 0.000 description 2
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 2
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 description 2
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 238000005821 Claisen rearrangement reaction Methods 0.000 description 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 238000005882 aldol condensation reaction Methods 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 238000007333 cyanation reaction Methods 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- 229910000039 hydrogen halide Inorganic materials 0.000 description 2
- 239000012433 hydrogen halide Substances 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000011968 lewis acid catalyst Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 159000000003 magnesium salts Chemical class 0.000 description 2
- 229910000000 metal hydroxide Inorganic materials 0.000 description 2
- 150000004692 metal hydroxides Chemical class 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 229910052762 osmium Inorganic materials 0.000 description 2
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 2
- 238000007248 oxidative elimination reaction Methods 0.000 description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 2
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- UOHMMEJUHBCKEE-UHFFFAOYSA-N prehnitene Chemical compound CC1=CC=C(C)C(C)=C1C UOHMMEJUHBCKEE-UHFFFAOYSA-N 0.000 description 2
- YKYONYBAUNKHLG-UHFFFAOYSA-N propyl acetate Chemical compound CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 2
- 125000005950 trichloromethanesulfonyloxy group Chemical group 0.000 description 2
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 description 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 150000000185 1,3-diols Chemical class 0.000 description 1
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 description 1
- MLRVZFYXUZQSRU-UHFFFAOYSA-N 1-chlorohexane Chemical compound CCCCCCCl MLRVZFYXUZQSRU-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical group [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
- GYHQXJTYSBEDPP-UHFFFAOYSA-N [1-(2-diphenylphosphanylnaphthalen-1-yl)naphthalen-2-yl]-diphenylphosphane;ruthenium Chemical group [Ru].C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 GYHQXJTYSBEDPP-UHFFFAOYSA-N 0.000 description 1
- NMLZYEWNUCRSRJ-UHFFFAOYSA-L [1-(2-diphenylphosphanylnaphthalen-1-yl)naphthalen-2-yl]-diphenylphosphane;ruthenium(2+);diacetate Chemical compound [Ru+2].CC([O-])=O.CC([O-])=O.C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 NMLZYEWNUCRSRJ-UHFFFAOYSA-L 0.000 description 1
- NARWRQCLGIIUSI-UHFFFAOYSA-K [Al+3].[Cl-].[Cl-].[Cl-].ClS(Cl)(=O)=O Chemical compound [Al+3].[Cl-].[Cl-].[Cl-].ClS(Cl)(=O)=O NARWRQCLGIIUSI-UHFFFAOYSA-K 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052977 alkali metal sulfide Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 1
- 125000005600 alkyl phosphonate group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 150000004808 allyl alcohols Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000005116 aryl carbamoyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 150000001555 benzenes Chemical group 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- UUYYJWFAHPQMJY-UHFFFAOYSA-N cyanomethoxy-oxido-oxophosphanium Chemical compound [O-][P+](=O)OCC#N UUYYJWFAHPQMJY-UHFFFAOYSA-N 0.000 description 1
- 150000004292 cyclic ethers Chemical group 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 150000002009 diols Chemical group 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 208000030172 endocrine system disease Diseases 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- XXROGKLTLUQVRX-UHFFFAOYSA-N hydroxymethylethylene Natural products OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- FGCWDTJSZOXWKL-UHFFFAOYSA-N n-[2-(1,2,3,7,8,9-hexahydropyrano[3,2-e]indol-1-yl)ethyl]butanamide Chemical compound O1CCCC2=C3C(CCNC(=O)CCC)CNC3=CC=C21 FGCWDTJSZOXWKL-UHFFFAOYSA-N 0.000 description 1
- JHWDRJFYVFNAEJ-UHFFFAOYSA-N n-[2-(1,2,3,7,8,9-hexahydropyrano[3,2-e]indol-1-yl)ethyl]propanamide Chemical compound O1CCCC2=C3C(CCNC(=O)CC)CNC3=CC=C21 JHWDRJFYVFNAEJ-UHFFFAOYSA-N 0.000 description 1
- OPZQTOCCEFLGEN-UHFFFAOYSA-N n-[2-(2,6,7,8-tetrahydro-1h-cyclopenta[e][1]benzofuran-8-yl)ethyl]butanamide Chemical compound C1=C2OCCC2=C2C(CCNC(=O)CCC)CCC2=C1 OPZQTOCCEFLGEN-UHFFFAOYSA-N 0.000 description 1
- YLXDSYKOBKBWJQ-UHFFFAOYSA-N n-[2-(2,6,7,8-tetrahydro-1h-cyclopenta[e][1]benzofuran-8-yl)ethyl]propanamide Chemical compound C1=C2OCCC2=C2C(CCNC(=O)CC)CCC2=C1 YLXDSYKOBKBWJQ-UHFFFAOYSA-N 0.000 description 1
- ZESOQCVBGGCKFO-UHFFFAOYSA-N n-[2-(2,6-dihydro-1h-cyclopenta[e][1]benzofuran-8-yl)ethyl]acetamide Chemical compound C1=C2OCCC2=C2C(CCNC(=O)C)=CCC2=C1 ZESOQCVBGGCKFO-UHFFFAOYSA-N 0.000 description 1
- KMJCPMOOTSDAPP-UHFFFAOYSA-N n-[2-(3,7,8,9-tetrahydropyrano[3,2-e]indol-1-yl)ethyl]propanamide Chemical compound O1CCCC2=C3C(CCNC(=O)CC)=CNC3=CC=C21 KMJCPMOOTSDAPP-UHFFFAOYSA-N 0.000 description 1
- ZXOBALCNSOLVQK-UHFFFAOYSA-N n-[2-(7-phenyl-2,6-dihydro-1h-cyclopenta[e][1]benzofuran-8-yl)ethyl]butanamide Chemical compound C1C2=CC=C3OCCC3=C2C(CCNC(=O)CCC)=C1C1=CC=CC=C1 ZXOBALCNSOLVQK-UHFFFAOYSA-N 0.000 description 1
- JCZMXVGQBBATMY-UHFFFAOYSA-N nitro acetate Chemical compound CC(=O)O[N+]([O-])=O JCZMXVGQBBATMY-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- ONTGMLYFJLDCPR-UHFFFAOYSA-M nitronium;trifluoromethanesulfonate Chemical compound O=[N+]=O.[O-]S(=O)(=O)C(F)(F)F ONTGMLYFJLDCPR-UHFFFAOYSA-M 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 150000004714 phosphonium salts Chemical group 0.000 description 1
- 210000004694 pigment cell Anatomy 0.000 description 1
- 210000004560 pineal gland Anatomy 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- DPLVEEXVKBWGHE-UHFFFAOYSA-N potassium sulfide Chemical compound [S-2].[K+].[K+] DPLVEEXVKBWGHE-UHFFFAOYSA-N 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 208000017443 reproductive system disease Diseases 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 229910001927 ruthenium tetroxide Inorganic materials 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- RODHHGZKXKDCJK-UHFFFAOYSA-J tetrachlorotitanium;2,2,2-trifluoroacetic acid Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ti+4].OC(=O)C(F)(F)F RODHHGZKXKDCJK-UHFFFAOYSA-J 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
-
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
-
- 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
- A61P15/18—Feminine 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
-
- 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
- C07D307/93—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 condensed with a ring other than six-membered
-
- 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
- C07D311/94—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 condensed with rings other than six-membered or with ring systems containing such rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/70—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with ring systems containing two or more relevant rings
-
- 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
-
- 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
- C07D491/04—Ortho-condensed systems
-
- 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
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pyrane Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Furan Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5149196 | 1996-03-08 | ||
| JP18366796 | 1996-07-12 | ||
| JP2918597 | 1997-02-13 | ||
| PCT/JP1997/000677 WO1997032871A1 (fr) | 1996-03-08 | 1997-03-05 | Composes tricycliques, leur production et leur utilisation |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO983970D0 NO983970D0 (no) | 1998-08-28 |
| NO983970L NO983970L (no) | 1998-08-28 |
| NO322205B1 true NO322205B1 (no) | 2006-08-28 |
Family
ID=27286462
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19983970A NO322205B1 (no) | 1996-03-08 | 1998-08-28 | Tricykliske forbindelser, deres fremstilling og anvendelse samt preparater inneholdende forbindelsene |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US6218429B1 (fr) |
| EP (2) | EP1550655A1 (fr) |
| JP (1) | JP4358917B2 (fr) |
| KR (1) | KR100494214B1 (fr) |
| CN (3) | CN100441574C (fr) |
| AT (1) | ATE219071T1 (fr) |
| CA (1) | CA2241666C (fr) |
| CZ (1) | CZ291626B6 (fr) |
| DE (1) | DE69713294T3 (fr) |
| DK (1) | DK0885210T5 (fr) |
| ES (1) | ES2175350T5 (fr) |
| HK (1) | HK1087112A1 (fr) |
| HU (1) | HU224220B1 (fr) |
| NO (1) | NO322205B1 (fr) |
| NZ (1) | NZ330656A (fr) |
| PL (1) | PL188093B1 (fr) |
| PT (1) | PT885210E (fr) |
| SK (1) | SK283970B6 (fr) |
| TW (1) | TW562803B (fr) |
| WO (1) | WO1997032871A1 (fr) |
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2773798B1 (fr) * | 1998-01-16 | 2001-02-02 | Adir | Nouveaux composes tricycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| AU4060599A (en) * | 1998-06-09 | 1999-12-30 | Takeda Chemical Industries Ltd. | Pharmaceutical composition for treating or preventing sleep disorders |
| DE60043017D1 (de) * | 1999-08-20 | 2009-11-05 | Takeda Pharmaceutical | Zusammensetzung für perkutane Absorption mit einem melantoninrezeptor-agonistisch wirkendem Wirkstoff |
| ATE293628T1 (de) * | 1999-08-20 | 2005-05-15 | Takeda Pharmaceutical | Dihydrobenzofuranderivate, verfahren zu ihrer herstellung und mittel |
| JP4632499B2 (ja) * | 1999-08-26 | 2011-02-16 | 武田薬品工業株式会社 | 鼻粘膜付着マトリックス |
| HU230234B1 (hu) * | 1999-09-08 | 2015-10-28 | Aventis Cropscience Uk Ltd. | Új herbicid készítmények |
| WO2002040053A1 (fr) * | 2000-11-17 | 2002-05-23 | Takeda Chemical Industries, Ltd. | Preparation pharmaceutique contenant du talc/ du sulfate de baryum |
| CA2428817C (fr) * | 2000-11-17 | 2010-06-01 | Takeda Chemical Industries, Ltd. | Preparation pharmaceutique contenant de la copolyvidone |
| US6800648B2 (en) * | 2001-04-26 | 2004-10-05 | Wyeth | Antipsychotic aminomethyl derivatives of 7,8-dihydro-3H-1,6,9-trioxa-3-AZA-cyclopenta[a]naphthalen-2-one |
| IL149377A (en) * | 2002-04-28 | 2012-10-31 | Neurim Pharma 1991 | Pharmaceutical formulation comprising melatonin for the potentiation of the effect of hypnotic compounds |
| TW200626137A (en) * | 2004-12-13 | 2006-08-01 | Takeda Pharmaceuticals Co | Preventive or therapeutic agent for sleep disorder |
| BRPI0607684A2 (pt) * | 2005-04-04 | 2009-09-22 | Takeda Pharmaceutical | composição farmacêutica, método para prevenir ou tratar distúrbios de depressão ou ansiedade, e, uso de (s)-n-[2-(1,6,7,8-tetraidro-2h-indeno[5,4-b]furan-8-il)-eti l]-propionamida |
| ES2366381T3 (es) * | 2005-06-22 | 2011-10-19 | Takeda Pharmaceutical Company Limited | Comprimido que contiene un ingrediente activo difícilmente soluble. |
| KR101187461B1 (ko) | 2005-07-29 | 2012-10-02 | 반다 파마슈티칼즈, 인코퍼레이티드. | 각성을 향상시키는 방법 |
| TW200803837A (en) | 2006-03-20 | 2008-01-16 | Takeda Pharmaceutical | Prophylactic or therapeutic agent for irritable bowel syndrome |
| TWI402261B (zh) * | 2006-06-19 | 2013-07-21 | Takeda Pharmaceutical | 三環化合物及其醫藥組成物 |
| CN101605795A (zh) * | 2006-12-08 | 2009-12-16 | 武田药品工业株式会社 | 三环化合物及其药物用途 |
| WO2008083204A2 (fr) * | 2006-12-28 | 2008-07-10 | Braincells, Inc. | Modulation de la neurogenèse par des ligands mélatoninergiques |
| US8247429B2 (en) | 2006-12-28 | 2012-08-21 | Takeda Pharmaceutical Company Limited | Tricyclic compound and pharmaceutical use thereof |
| EP2139845A1 (fr) * | 2007-02-26 | 2010-01-06 | Teva Pharmaceutical Industries Ltd. | Intermédiaires et procédés pour la synthèse de ramelteon |
| EA200971003A1 (ru) | 2007-04-26 | 2010-04-30 | Такеда Фармасьютикал Компани Лимитед | Бициклическое соединение и его фармацевтическое применение |
| EP2098519A1 (fr) | 2007-05-31 | 2009-09-09 | Teva Pharmaceutical Industries Ltd. | Procédé de synthèse du rameltéon et ses intermédiaires |
| WO2009060318A2 (fr) * | 2007-07-12 | 2009-05-14 | Teva Pharmaceutical Industries Ltd. | Formes polymorphes de rameltéon et leurs procédés de préparation |
| ES2324849A1 (es) * | 2007-10-25 | 2009-08-17 | Ferrer Internacional, S.A. | Compuestos de indano. |
| US7470814B1 (en) * | 2007-10-31 | 2008-12-30 | Ferrer Internacional, S.A. | Process for the preparation of substituted 7-allyl-6-hydroxy-indanes |
| WO2009056993A2 (fr) * | 2007-11-01 | 2009-05-07 | Teva Pharmaceutical Industries Ltd. | Procédé de synthèse de rameltéon et intermédiaires de ce dernier |
| SG185969A1 (en) * | 2008-01-31 | 2012-12-28 | Takeda Pharmaceutical | Prophylactic or therapeutic agent for attention deficit/hyperactivity disorder |
| WO2009118714A2 (fr) | 2008-03-28 | 2009-10-01 | Ecolab Inc. | Acides peroxycarboxyliques sulfurés, leur préparation et leurs procédés d’utilisation en tant qu’agents de blanchiment et antimicrobiens |
| US8871807B2 (en) | 2008-03-28 | 2014-10-28 | Ecolab Usa Inc. | Detergents capable of cleaning, bleaching, sanitizing and/or disinfecting textiles including sulfoperoxycarboxylic acids |
| US8809392B2 (en) | 2008-03-28 | 2014-08-19 | Ecolab Usa Inc. | Sulfoperoxycarboxylic acids, their preparation and methods of use as bleaching and antimicrobial agents |
| AU2009275918A1 (en) | 2008-07-30 | 2010-02-04 | Ferrer Internacional S. A. | 1,6-dihydro-2H-3-oxa-6-aza-as-indacene compounds |
| WO2010045565A1 (fr) * | 2008-10-16 | 2010-04-22 | Teva Pharmaceutical Industries Ltd. | Procédé de synthèse du ramelteon et de ses intermédiaires |
| EP2344468A4 (fr) * | 2008-11-14 | 2012-08-01 | Watson Pharma Private Ltd | Procédé de préparation de rameltéon |
| US8555875B2 (en) | 2008-12-23 | 2013-10-15 | Map Pharmaceuticals, Inc. | Inhalation devices and related methods for administration of sedative hypnotic compounds |
| WO2010092107A1 (fr) | 2009-02-12 | 2010-08-19 | Lek Pharmaceuticals D.D. | Synthèse de (s)-n-[2-(1,6,7,8-tétrahydro-2h-indéno-[5,4-b]furan-8-yl)éthyl]propionamide |
| CA2754802A1 (fr) * | 2009-03-10 | 2010-09-16 | Industriale Chimica S.R.L. | Procede de preparation du ramelteon |
| EP2243775A1 (fr) | 2009-04-07 | 2010-10-27 | LEK Pharmaceuticals d.d. | Synthèse de 1-(2,3-dihydrobenzofuran-4-YL)éthanone en tant qu'intermédiaire dans la préparation de rameltéon |
| EP2483258A1 (fr) * | 2009-09-29 | 2012-08-08 | Lonza Ltd. | Procédé de préparation de 1,2,6,7-tétrahydro-8h-indeno[5,4-b]furan-8-one |
| JP5758395B2 (ja) * | 2009-10-15 | 2015-08-05 | ザ チルドレンズ メディカル センター コーポレイション | 疼痛を治療するためのセピアプテリンレダクターゼ阻害薬 |
| WO2012035303A2 (fr) | 2010-09-17 | 2012-03-22 | Cipla Limited Et Al | Nouveau procédé de synthèse du ramelteon et intermédiaires clés pour la synthèse du ramelteon |
| CN102321056B (zh) * | 2011-07-29 | 2014-05-14 | 宁波人健药业集团股份有限公司 | 一种合成雷美替胺的方法 |
| CN102391220A (zh) * | 2011-10-10 | 2012-03-28 | 四川大学 | 三环乙醇类化合物及其制备方法和用途 |
| US9321664B2 (en) | 2011-12-20 | 2016-04-26 | Ecolab Usa Inc. | Stable percarboxylic acid compositions and uses thereof |
| US9242879B2 (en) | 2012-03-30 | 2016-01-26 | Ecolab Usa Inc. | Use of peracetic acid/hydrogen peroxide and peroxide-reducing agents for treatment of drilling fluids, frac fluids, flowback water and disposal water |
| EP2884275A4 (fr) | 2012-07-10 | 2016-04-13 | Astellas Pharma Inc | Composition pharmaceutique destinée à traiter ou à prévenir l'incontinence urinaire de stress ou l'incontinence mixte, et procédé de criblage pour identifier les composés à inclure dans ladite composition pharmaceutique |
| AR091699A1 (es) | 2012-07-10 | 2015-02-25 | Astellas Pharma Inc | Derivado de indol carboxamida |
| CN103724357B (zh) * | 2012-10-11 | 2016-06-08 | 中国药科大学 | 一种3,4-二氢吡喃并[3,2-b]吲哚-2-酮类化合物的合成方法 |
| CN102924410A (zh) * | 2012-10-29 | 2013-02-13 | 华润赛科药业有限责任公司 | 一种雷美替胺的制备方法及其中间体 |
| US8822719B1 (en) | 2013-03-05 | 2014-09-02 | Ecolab Usa Inc. | Peroxycarboxylic acid compositions suitable for inline optical or conductivity monitoring |
| US20140256811A1 (en) | 2013-03-05 | 2014-09-11 | Ecolab Usa Inc. | Efficient stabilizer in controlling self accelerated decomposition temperature of peroxycarboxylic acid compositions with mineral acids |
| US10165774B2 (en) | 2013-03-05 | 2019-01-01 | Ecolab Usa Inc. | Defoamer useful in a peracid composition with anionic surfactants |
| CA2934825A1 (fr) | 2014-01-14 | 2015-07-23 | Shunichiro Matsumoto | Compose indole |
| AU2017205722B2 (en) | 2016-01-08 | 2022-02-17 | Takeda Pharmaceutical Company Limited | Prophylactic or therapeutic agent for autism spectrum disorder |
| WO2017119456A1 (fr) | 2016-01-08 | 2017-07-13 | 武田薬品工業株式会社 | Agent de traitement prophylactique ou thérapeutique du délire |
| WO2021026410A1 (fr) | 2019-08-07 | 2021-02-11 | Ecolab Usa Inc. | Chélateurs à support solide et polymère pour la stabilisation de compositions contenant un peracide |
| CN110776485B (zh) * | 2019-11-22 | 2022-09-30 | 山东邹平大展新材料有限公司 | 一种雷美替胺杂质的制备方法 |
| WO2023059546A1 (fr) * | 2021-10-04 | 2023-04-13 | Psilosterics, Llc | Agonistes du récepteur de la sérotonine et leurs méthodes de fabrication et d'utilisation |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2680366B1 (fr) * | 1991-08-13 | 1995-01-20 | Adir | Nouveaux derives d'arylethylamines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
| FR2681862B1 (fr) | 1991-09-27 | 1993-11-12 | Adir Cie | Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent. |
| FR2713636B1 (fr) | 1993-12-07 | 1996-01-05 | Adir | Nouveaux dérivés naphtaléniques, leur procédé de préparation, et les compositions pharmaceutiques qui les contiennent. |
| GB9326192D0 (en) * | 1993-12-22 | 1994-02-23 | Glaxo Group Ltd | Chemical compounds |
| GB9407919D0 (en) * | 1994-04-21 | 1994-06-15 | Glaxo Group Ltd | Chemical compounds |
| FR2725985B1 (fr) * | 1994-10-21 | 1996-11-15 | Adir | Nouveaux composes tricycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US5661186A (en) | 1995-02-24 | 1997-08-26 | Bristol-Myers Squibb Co. | Tetralinyl-and indanyl-ethylamides |
-
1997
- 1997-03-05 HU HU9900616A patent/HU224220B1/hu active IP Right Grant
- 1997-03-05 EP EP04027766A patent/EP1550655A1/fr not_active Withdrawn
- 1997-03-05 PL PL97328726A patent/PL188093B1/pl unknown
- 1997-03-05 ES ES97905450T patent/ES2175350T5/es not_active Expired - Lifetime
- 1997-03-05 CN CNB2005100916061A patent/CN100441574C/zh not_active Expired - Lifetime
- 1997-03-05 EP EP97905450A patent/EP0885210B2/fr not_active Expired - Lifetime
- 1997-03-05 KR KR10-1998-0707080A patent/KR100494214B1/ko not_active IP Right Cessation
- 1997-03-05 CZ CZ19982775A patent/CZ291626B6/cs not_active IP Right Cessation
- 1997-03-05 DE DE69713294T patent/DE69713294T3/de not_active Expired - Lifetime
- 1997-03-05 DK DK97905450T patent/DK0885210T5/da active
- 1997-03-05 SK SK1150-98A patent/SK283970B6/sk not_active IP Right Cessation
- 1997-03-05 PT PT97905450T patent/PT885210E/pt unknown
- 1997-03-05 CN CNB971927006A patent/CN100443480C/zh not_active Expired - Lifetime
- 1997-03-05 WO PCT/JP1997/000677 patent/WO1997032871A1/fr active IP Right Grant
- 1997-03-05 CA CA002241666A patent/CA2241666C/fr not_active Expired - Lifetime
- 1997-03-05 CN CNA200610100063XA patent/CN1900067A/zh active Pending
- 1997-03-05 AT AT97905450T patent/ATE219071T1/de active
- 1997-03-05 NZ NZ330656A patent/NZ330656A/xx not_active IP Right Cessation
- 1997-03-06 TW TW086102717A patent/TW562803B/zh not_active IP Right Cessation
-
1998
- 1998-08-28 NO NO19983970A patent/NO322205B1/no not_active IP Right Cessation
- 1998-09-22 JP JP26811098A patent/JP4358917B2/ja not_active Expired - Lifetime
-
1999
- 1999-05-10 US US09/309,519 patent/US6218429B1/en not_active Expired - Lifetime
-
2006
- 2006-06-28 HK HK06107304.0A patent/HK1087112A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO322205B1 (no) | Tricykliske forbindelser, deres fremstilling og anvendelse samt preparater inneholdende forbindelsene | |
| US6034239A (en) | Tricyclic compounds, their production and use | |
| US20070015802A1 (en) | Inhibitors of cyclin dependent kinases and their use | |
| JP2884153B2 (ja) | 三環性化合物、その製造法および剤 | |
| EP2100895B1 (fr) | Composé tricyclique et son utilisation médicale | |
| EP2029561B1 (fr) | Composé tricyclique et utilisation pharmaceutique de celui-ci | |
| NO851010L (no) | Substituerte benzopyraner, fremgangsmaate til deres fremstilling, samt deres anvendelse i legemidler | |
| EP1238973A1 (fr) | Nouveaux composes tricycliques substitues | |
| JPH093068A (ja) | ベンズイソチアゾリル置換アミノメチルクロマン | |
| WO2001014384A1 (fr) | Derives dihydrobenzofuran tricycliques, leur procede de preparation et agents | |
| AU616608B2 (en) | 4,5,6,7-tetrasubstituted benzoxazolones | |
| KR20020074420A (ko) | 인데노인돌론 화합물, 이의 제조 방법 및 이를 함유하는약제 조성물 | |
| KR20050042192A (ko) | 헤테로고리-접합된 벤조디옥산의 항울성 피페리딘 유도체 | |
| EP1199304A1 (fr) | Composés bicycliques et composition pharmaceutique contenant un composé tricyclique pour le traitement ou la prévention de troubles de sommeil | |
| AU706610C (en) | Tricyclic compounds, their production and use | |
| US5416209A (en) | 5,6-dihydro-dibenz[b,e]azepine-6,11-dione-11-oximes | |
| US9771325B2 (en) | Tricyclic compounds and preparation thereof | |
| WO2001014385A1 (fr) | Derives de dihydrobenzofuran, leur procede de preparation et agents | |
| NO973442L (no) | Nye bismidforbindelser, fremgangsmåte ved fremstilling derav og farmasöytiske sammensetninger inneholdende slike | |
| JP2000044572A (ja) | 新規８Ｈ―チエノ―〔２，３―ｂ〕ピロリジン―８―オン化合物、その製造の方法及びそれらを含む医薬組成物 | |
| JP2001131179A (ja) | 三環性ジヒドロフラン誘導体、その製造法及び剤 | |
| JP2001131180A (ja) | ジヒドロベンゾフラン誘導体、その製造法及び剤 | |
| FR2722196A1 (fr) | Nouveaux derives amines de 1,3-dihydro-2h-pyrrolo(2,3-b) pyridin-2-ones et oxazolo(4,5-b) pyridin-2 (3h)-ones, leur procede de preparation et les compositions pharmaceutique qui les contiennent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |