DE2113455A1 - Verfahren zur Herstellung von neuen Aryloxy- und Arylthioalkansaeuren,ihren Salzen und funktionellen Derivaten - Google Patents
Verfahren zur Herstellung von neuen Aryloxy- und Arylthioalkansaeuren,ihren Salzen und funktionellen DerivatenInfo
- Publication number
- DE2113455A1 DE2113455A1 DE19712113455 DE2113455A DE2113455A1 DE 2113455 A1 DE2113455 A1 DE 2113455A1 DE 19712113455 DE19712113455 DE 19712113455 DE 2113455 A DE2113455 A DE 2113455A DE 2113455 A1 DE2113455 A1 DE 2113455A1
- Authority
- DE
- Germany
- Prior art keywords
- tetrahydro
- dibenzofuran
- acid
- mmol
- yloxy
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 239000002253 acid Substances 0.000 title claims description 72
- 238000000034 method Methods 0.000 title claims description 42
- 150000003839 salts Chemical class 0.000 title claims description 28
- 150000007513 acids Chemical class 0.000 title claims description 26
- 125000004104 aryloxy group Chemical group 0.000 title claims description 21
- 238000002360 preparation method Methods 0.000 title claims description 12
- -1 alkali metal salt Chemical class 0.000 claims description 208
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 134
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 52
- 150000001875 compounds Chemical class 0.000 claims description 44
- 150000002148 esters Chemical class 0.000 claims description 38
- 239000003513 alkali Substances 0.000 claims description 30
- 150000002825 nitriles Chemical class 0.000 claims description 22
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 16
- 150000001408 amides Chemical class 0.000 claims description 16
- 229910052783 alkali metal Inorganic materials 0.000 claims description 15
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 13
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 9
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 9
- 239000011707 mineral Substances 0.000 claims description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000005907 alkyl ester group Chemical group 0.000 claims description 7
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- AOIBRDYGMJIGRN-UHFFFAOYSA-N 2-(6,7,8,9-tetrahydrodibenzothiophen-3-yloxy)octanoic acid Chemical compound C1=CC(=CC=2SC3=C(C21)CCCC3)OC(C(=O)O)CCCCCC AOIBRDYGMJIGRN-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- QPWMVKSUTLRMHE-UHFFFAOYSA-N 2-(6,7,8,9-tetrahydrodibenzofuran-3-yloxy)octanoic acid Chemical compound C1=CC(=CC=2OC3=C(C21)CCCC3)OC(C(=O)O)CCCCCC QPWMVKSUTLRMHE-UHFFFAOYSA-N 0.000 claims description 5
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 5
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 5
- 150000002576 ketones Chemical class 0.000 claims description 5
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 5
- AQIRJHCIAYPEPN-UHFFFAOYSA-N 2-(6,7,8,9-tetrahydrodibenzofuran-2-yloxy)dodecanoic acid Chemical compound C1=C(C=CC=2OC3=C(C21)CCCC3)OC(C(=O)O)CCCCCCCCCC AQIRJHCIAYPEPN-UHFFFAOYSA-N 0.000 claims description 4
- HMPKFOIJXCWTOV-UHFFFAOYSA-N 2-(6,7,8,9-tetrahydrodibenzofuran-3-ylsulfanyl)dodecanoic acid Chemical compound C1=CC(=CC=2OC3=C(C21)CCCC3)SC(C(=O)O)CCCCCCCCCC HMPKFOIJXCWTOV-UHFFFAOYSA-N 0.000 claims description 4
- KQXVBULMXCKYDK-UHFFFAOYSA-N 2-(6,7,8,9-tetrahydrodibenzofuran-3-ylsulfanyl)octanoic acid Chemical compound C1=CC(=CC=2OC3=C(C21)CCCC3)SC(C(=O)O)CCCCCC KQXVBULMXCKYDK-UHFFFAOYSA-N 0.000 claims description 4
- QIJPGKNWNLOTNE-UHFFFAOYSA-N 2-(6,7,8,9-tetrahydrodibenzothiophen-3-ylsulfanyl)octanoic acid Chemical compound C1=CC(=CC=2SC3=C(C21)CCCC3)SC(C(=O)O)CCCCCC QIJPGKNWNLOTNE-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 239000001569 carbon dioxide Substances 0.000 claims description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- AFOMMDYUQVGYGC-UHFFFAOYSA-N 2-(6,7,8,9-tetrahydrodibenzofuran-3-yloxy)dodecanoic acid Chemical compound C1=CC(=CC=2OC3=C(C21)CCCC3)OC(C(=O)O)CCCCCCCCCC AFOMMDYUQVGYGC-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- DRRWVTCZVGIBLE-UHFFFAOYSA-N ethyl 2-(6,7,8,9-tetrahydrodibenzofuran-2-yloxy)heptanoate Chemical compound C(C)OC(C(CCCCC)OC1=CC2=C(OC3=C2CCCC3)C=C1)=O DRRWVTCZVGIBLE-UHFFFAOYSA-N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000002560 nitrile group Chemical group 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 208000027697 autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 279
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 208
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 173
- 239000000243 solution Substances 0.000 description 142
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 123
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 91
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 76
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 72
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 66
- 238000010992 reflux Methods 0.000 description 63
- 239000011541 reaction mixture Substances 0.000 description 55
- 238000002844 melting Methods 0.000 description 53
- 230000008018 melting Effects 0.000 description 53
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 44
- 238000001816 cooling Methods 0.000 description 43
- 238000001035 drying Methods 0.000 description 42
- 239000000741 silica gel Substances 0.000 description 41
- 229910002027 silica gel Inorganic materials 0.000 description 41
- DLFLWVYSSLYVBK-UHFFFAOYSA-N 6,7,8,9-tetrahydrodibenzofuran-2-ol Chemical compound C1CCCC2=C1OC1=CC=C(O)C=C12 DLFLWVYSSLYVBK-UHFFFAOYSA-N 0.000 description 38
- 229910052757 nitrogen Inorganic materials 0.000 description 37
- 239000002904 solvent Substances 0.000 description 37
- 239000007858 starting material Substances 0.000 description 36
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 35
- 235000019341 magnesium sulphate Nutrition 0.000 description 35
- 239000000203 mixture Substances 0.000 description 34
- 238000003756 stirring Methods 0.000 description 34
- 239000003921 oil Substances 0.000 description 33
- 230000007935 neutral effect Effects 0.000 description 32
- 229960000583 acetic acid Drugs 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 239000012071 phase Substances 0.000 description 27
- 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 26
- 238000004440 column chromatography Methods 0.000 description 26
- 239000011734 sodium Substances 0.000 description 26
- 239000012362 glacial acetic acid Substances 0.000 description 25
- 229910052708 sodium Inorganic materials 0.000 description 25
- RJPHJNSOVWUNLF-UHFFFAOYSA-N 2-(6,7,8,9-tetrahydrodibenzofuran-2-yloxy)octanoic acid Chemical compound C1=C(C=CC=2OC3=C(C21)CCCC3)OC(C(=O)O)CCCCCC RJPHJNSOVWUNLF-UHFFFAOYSA-N 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 21
- 239000012043 crude product Substances 0.000 description 20
- IPESETNMSBOYDM-UHFFFAOYSA-N 6,7,8,9-tetrahydrodibenzofuran-2-thiol Chemical compound C1=C(C=CC=2OC3=C(C21)CCCC3)S IPESETNMSBOYDM-UHFFFAOYSA-N 0.000 description 19
- NZQLDDRKACJBHY-UHFFFAOYSA-N 6,7,8,9-tetrahydrodibenzofuran-3-ol Chemical compound C1CCCC2=C1C1=CC=C(O)C=C1O2 NZQLDDRKACJBHY-UHFFFAOYSA-N 0.000 description 19
- 238000010828 elution Methods 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 18
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 150000001735 carboxylic acids Chemical class 0.000 description 16
- 239000007789 gas Substances 0.000 description 16
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 16
- QANXKDIOWPLAHH-UHFFFAOYSA-N 6,7,8,9-tetrahydrodibenzofuran-3-thiol Chemical compound C1=CC(=CC=2OC3=C(C21)CCCC3)S QANXKDIOWPLAHH-UHFFFAOYSA-N 0.000 description 15
- LWSQNKUPPZYRGH-UHFFFAOYSA-N 6,7,8,9-tetrahydrodibenzothiophene-2-thiol Chemical compound C1=C(C=CC=2SC3=C(C21)CCCC3)S LWSQNKUPPZYRGH-UHFFFAOYSA-N 0.000 description 14
- 235000011121 sodium hydroxide Nutrition 0.000 description 14
- PKJAPNISIINOOB-UHFFFAOYSA-N 6,7,8,9-tetrahydrodibenzothiophen-2-ol Chemical compound C1=C(C=CC=2SC3=C(C21)CCCC3)O PKJAPNISIINOOB-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 13
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 12
- SWUWAMMQSPMFKF-UHFFFAOYSA-N 6,7,8,9-tetrahydrodibenzothiophen-3-ol Chemical compound C1CCCC2=C1C1=CC=C(O)C=C1S2 SWUWAMMQSPMFKF-UHFFFAOYSA-N 0.000 description 11
- 238000009835 boiling Methods 0.000 description 11
- 239000013078 crystal Substances 0.000 description 11
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- LREHXNMBUBVFHA-UHFFFAOYSA-N 1,2,3,4-tetrahydrodibenzofuran Chemical compound O1C2=CC=CC=C2C2=C1CCCC2 LREHXNMBUBVFHA-UHFFFAOYSA-N 0.000 description 10
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 10
- 125000004494 ethyl ester group Chemical group 0.000 description 10
- 238000001953 recrystallisation Methods 0.000 description 10
- 238000005406 washing Methods 0.000 description 10
- JCLPOPNXITXHOR-UHFFFAOYSA-N 1,2,3,4-tetrahydrodibenzothiophene Chemical compound S1C2=CC=CC=C2C2=C1CCCC2 JCLPOPNXITXHOR-UHFFFAOYSA-N 0.000 description 9
- ZNLGDZWIVKXSBA-UHFFFAOYSA-N 2-(6,7,8,9-tetrahydrodibenzothiophen-2-yloxy)octanoic acid Chemical compound C1=C(C=CC=2SC3=C(C21)CCCC3)OC(C(=O)O)CCCCCC ZNLGDZWIVKXSBA-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 9
- 239000012230 colorless oil Substances 0.000 description 9
- VCNVCTNYSFIDOO-UHFFFAOYSA-N diethyl 2-bromo-2-hexylpropanedioate Chemical compound CCCCCCC(Br)(C(=O)OCC)C(=O)OCC VCNVCTNYSFIDOO-UHFFFAOYSA-N 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- 159000000000 sodium salts Chemical class 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- GZHNWRYYMJCHBM-UHFFFAOYSA-N 2-(6,7,8,9-tetrahydrodibenzofuran-2-yloxy)heptanoic acid Chemical compound C1=C(C=CC=2OC3=C(C21)CCCC3)OC(C(=O)O)CCCCC GZHNWRYYMJCHBM-UHFFFAOYSA-N 0.000 description 8
- JDMQBSZGCYBGAQ-UHFFFAOYSA-N 2-(6,7,8,9-tetrahydrodibenzofuran-2-ylsulfanyl)octanoic acid Chemical compound C1=C(C=CC=2OC3=C(C21)CCCC3)SC(C(=O)O)CCCCCC JDMQBSZGCYBGAQ-UHFFFAOYSA-N 0.000 description 8
- GTGTXZRPJHDASG-UHFFFAOYSA-N 2-bromooctanoic acid Chemical compound CCCCCCC(Br)C(O)=O GTGTXZRPJHDASG-UHFFFAOYSA-N 0.000 description 8
- JHBMPQFJFJKMFS-UHFFFAOYSA-N 6,7,8,9-tetrahydrodibenzothiophene-3-thiol Chemical compound C1=CC(=CC=2SC3=C(C21)CCCC3)S JHBMPQFJFJKMFS-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 8
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 235000010755 mineral Nutrition 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 239000012259 ether extract Substances 0.000 description 7
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 7
- 239000000155 melt Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 6
- 159000000007 calcium salts Chemical class 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- IOLQWGVDEFWYNP-UHFFFAOYSA-N ethyl 2-bromo-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)Br IOLQWGVDEFWYNP-UHFFFAOYSA-N 0.000 description 6
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 229920000159 gelatin Polymers 0.000 description 6
- 235000019322 gelatine Nutrition 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000012429 reaction media Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 239000000454 talc Substances 0.000 description 6
- 229910052623 talc Inorganic materials 0.000 description 6
- MNDIARAMWBIKFW-UHFFFAOYSA-N 1-bromohexane Chemical compound CCCCCCBr MNDIARAMWBIKFW-UHFFFAOYSA-N 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- 150000001447 alkali salts Chemical class 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 5
- VGYZSIMAKGWWOP-UHFFFAOYSA-N ethyl 2-bromododecanoate Chemical compound CCCCCCCCCCC(Br)C(=O)OCC VGYZSIMAKGWWOP-UHFFFAOYSA-N 0.000 description 5
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000000061 acid fraction Substances 0.000 description 2
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000001649 bromium compounds Chemical class 0.000 description 2
- KDPAWGWELVVRCH-UHFFFAOYSA-N bromoacetic acid Chemical compound OC(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- NXAVOIHNEHIXBG-UHFFFAOYSA-N diethyl 2-hexyl-2-(6,7,8,9-tetrahydrodibenzothiophen-3-ylsulfanyl)propanedioate Chemical compound C(C)OC(C(C(=O)OCC)(CCCCCC)SC=1C=CC2=C(SC3=C2CCCC3)C1)=O NXAVOIHNEHIXBG-UHFFFAOYSA-N 0.000 description 2
- UPQZOUHVTJNGFK-UHFFFAOYSA-N diethyl 2-methylpropanedioate Chemical compound CCOC(=O)C(C)C(=O)OCC UPQZOUHVTJNGFK-UHFFFAOYSA-N 0.000 description 2
- PMLHYEQTZIFKMD-UHFFFAOYSA-N diethyl 2-tetradecyl-2-(6,7,8,9-tetrahydrodibenzofuran-3-ylsulfanyl)propanedioate Chemical compound C(C)OC(C(C(=O)OCC)(CCCCCCCCCCCCCC)SC=1C=CC2=C(OC3=C2CCCC3)C1)=O PMLHYEQTZIFKMD-UHFFFAOYSA-N 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
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- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
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- 230000000694 effects Effects 0.000 description 2
- UZHSPLZWMUFOKV-UHFFFAOYSA-N ethyl 2-(6,7,8,9-tetrahydrodibenzofuran-2-yloxy)dodecanoate Chemical compound C(C)OC(C(CCCCCCCCCC)OC1=CC2=C(OC3=C2CCCC3)C=C1)=O UZHSPLZWMUFOKV-UHFFFAOYSA-N 0.000 description 2
- VPWIQUHAZFGHIN-UHFFFAOYSA-N ethyl 2-(6,7,8,9-tetrahydrodibenzofuran-2-yloxy)octanoate Chemical compound C(C)OC(C(CCCCCC)OC1=CC2=C(OC3=C2CCCC3)C=C1)=O VPWIQUHAZFGHIN-UHFFFAOYSA-N 0.000 description 2
- YDIDLMYXFIUJCO-UHFFFAOYSA-N ethyl 2-(6,7,8,9-tetrahydrodibenzofuran-2-ylsulfanyl)octanoate Chemical compound C(C)OC(C(CCCCCC)SC1=CC2=C(OC3=C2CCCC3)C=C1)=O YDIDLMYXFIUJCO-UHFFFAOYSA-N 0.000 description 2
- QZTDRTFPUGYAEB-UHFFFAOYSA-N ethyl 2-(6,7,8,9-tetrahydrodibenzofuran-3-yloxy)dodecanoate Chemical compound C(C)OC(C(CCCCCCCCCC)OC=1C=CC2=C(OC3=C2CCCC3)C1)=O QZTDRTFPUGYAEB-UHFFFAOYSA-N 0.000 description 2
- MHNXBAJGPLEKMR-UHFFFAOYSA-N ethyl 2-(6,7,8,9-tetrahydrodibenzothiophen-2-yloxy)octanoate Chemical compound C(C)OC(C(CCCCCC)OC1=CC2=C(SC3=C2CCCC3)C=C1)=O MHNXBAJGPLEKMR-UHFFFAOYSA-N 0.000 description 2
- RJTBLJNHBFLWFN-UHFFFAOYSA-N ethyl 2-(6,7,8,9-tetrahydrodibenzothiophen-3-yloxy)hexadecanoate Chemical compound C(C)OC(C(CCCCCCCCCCCCCC)OC=1C=CC2=C(SC3=C2CCCC3)C1)=O RJTBLJNHBFLWFN-UHFFFAOYSA-N 0.000 description 2
- WJGFHJCJABTNPO-UHFFFAOYSA-N ethyl 2-cyano-2-(6,7,8,9-tetrahydrodibenzothiophen-3-yloxy)heptanoate Chemical compound C(C)OC(C(CCCCC)(OC=1C=CC2=C(SC3=C2CCCC3)C1)C#N)=O WJGFHJCJABTNPO-UHFFFAOYSA-N 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- TVQGDYNRXLTQAP-UHFFFAOYSA-N ethyl heptanoate Chemical compound CCCCCCC(=O)OCC TVQGDYNRXLTQAP-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
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- 150000002430 hydrocarbons Chemical class 0.000 description 2
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- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000005661 deetherification reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- OVIJXMCMCXEGHO-UHFFFAOYSA-N dibenzofuran-3-thiol Chemical compound C1=CC=C2C3=CC=C(S)C=C3OC2=C1 OVIJXMCMCXEGHO-UHFFFAOYSA-N 0.000 description 1
- KBASHUUJJGWTIH-UHFFFAOYSA-N diethyl 2-bromo-2-decylpropanedioate Chemical compound C(C)OC(C(C(=O)OCC)(CCCCCCCCCC)Br)=O KBASHUUJJGWTIH-UHFFFAOYSA-N 0.000 description 1
- CVYHCDDNYIZWQA-UHFFFAOYSA-N diethyl 2-hexyl-2-(6,7,8,9-tetrahydrodibenzothiophen-2-ylsulfanyl)propanedioate Chemical compound C(C)OC(C(C(=O)OCC)(CCCCCC)SC1=CC2=C(SC3=C2CCCC3)C=C1)=O CVYHCDDNYIZWQA-UHFFFAOYSA-N 0.000 description 1
- GHYAZTGZUDNEJQ-UHFFFAOYSA-N diethyl 2-hexyl-2-(6,7,8,9-tetrahydrodibenzothiophen-3-yloxy)propanedioate Chemical compound C(C)OC(C(C(=O)OCC)(CCCCCC)OC=1C=CC2=C(SC3=C2CCCC3)C1)=O GHYAZTGZUDNEJQ-UHFFFAOYSA-N 0.000 description 1
- DSGUYHWHKYWRDG-UHFFFAOYSA-N diethyl 2-tetradecyl-2-(6,7,8,9-tetrahydrodibenzofuran-2-yloxy)propanedioate Chemical compound C(C)OC(C(C(=O)OCC)(CCCCCCCCCCCCCC)OC1=CC2=C(OC3=C2CCCC3)C=C1)=O DSGUYHWHKYWRDG-UHFFFAOYSA-N 0.000 description 1
- GESHRHVYCSRGQP-UHFFFAOYSA-N diethyl 2-tetradecylpropanedioate Chemical compound CCCCCCCCCCCCCCC(C(=O)OCC)C(=O)OCC GESHRHVYCSRGQP-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- MYAAUYFTXWCGSB-UHFFFAOYSA-N ethyl 2-(6,7,8,9-tetrahydrodibenzofuran-2-yloxy)decanoate Chemical compound C(C)OC(C(CCCCCCCC)OC1=CC2=C(OC3=C2CCCC3)C=C1)=O MYAAUYFTXWCGSB-UHFFFAOYSA-N 0.000 description 1
- WODQEQQCVCRNQP-UHFFFAOYSA-N ethyl 2-(6,7,8,9-tetrahydrodibenzofuran-2-yloxy)hexadecanoate Chemical compound C(C)OC(C(CCCCCCCCCCCCCC)OC1=CC2=C(OC3=C2CCCC3)C=C1)=O WODQEQQCVCRNQP-UHFFFAOYSA-N 0.000 description 1
- HCXBWQQLOZGEOX-UHFFFAOYSA-N ethyl 2-(6,7,8,9-tetrahydrodibenzofuran-2-yloxy)pentanoate Chemical compound C(C)OC(C(CCC)OC1=CC2=C(OC3=C2CCCC3)C=C1)=O HCXBWQQLOZGEOX-UHFFFAOYSA-N 0.000 description 1
- PVXGSCIZBRFHSD-UHFFFAOYSA-N ethyl 2-(6,7,8,9-tetrahydrodibenzofuran-3-yloxy)octanoate Chemical compound C(C)OC(C(CCCCCC)OC=1C=CC2=C(OC3=C2CCCC3)C1)=O PVXGSCIZBRFHSD-UHFFFAOYSA-N 0.000 description 1
- RUXWKPXVWREZRF-UHFFFAOYSA-N ethyl 2-bromo-2-cyanooctanoate Chemical compound C(C)OC(C(CCCCCC)(Br)C#N)=O RUXWKPXVWREZRF-UHFFFAOYSA-N 0.000 description 1
- SXZHDULBCLKRAE-UHFFFAOYSA-N ethyl 2-bromo-5-methylhexanoate Chemical compound CCOC(=O)C(Br)CCC(C)C SXZHDULBCLKRAE-UHFFFAOYSA-N 0.000 description 1
- XIMFCGSNSKXPBO-UHFFFAOYSA-N ethyl 2-bromobutanoate Chemical compound CCOC(=O)C(Br)CC XIMFCGSNSKXPBO-UHFFFAOYSA-N 0.000 description 1
- IOOXHTJCOQWOJW-UHFFFAOYSA-N ethyl 2-bromodecanoate Chemical compound CCCCCCCCC(Br)C(=O)OCC IOOXHTJCOQWOJW-UHFFFAOYSA-N 0.000 description 1
- ORSIRXYHFPHWTN-UHFFFAOYSA-N ethyl 2-bromopentanoate Chemical compound CCCC(Br)C(=O)OCC ORSIRXYHFPHWTN-UHFFFAOYSA-N 0.000 description 1
- BECPIDTWFHVKLU-UHFFFAOYSA-N ethyl 2-cyano-2-(6,7,8,9-tetrahydrodibenzofuran-3-yloxy)octanoate Chemical compound C(C)OC(C(CCCCCC)(OC=1C=CC2=C(OC3=C2CCCC3)C1)C#N)=O BECPIDTWFHVKLU-UHFFFAOYSA-N 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
- OKMWRBGVXIVCNF-UHFFFAOYSA-N ethyl 2-cyanoheptanoate Chemical compound CCCCCC(C#N)C(=O)OCC OKMWRBGVXIVCNF-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- WDAXFOBOLVPGLV-UHFFFAOYSA-N ethyl isobutyrate Chemical compound CCOC(=O)C(C)C WDAXFOBOLVPGLV-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 229910021485 fumed silica Inorganic materials 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- AEDIXYWIVPYNBI-UHFFFAOYSA-N heptanamide Chemical compound CCCCCCC(N)=O AEDIXYWIVPYNBI-UHFFFAOYSA-N 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- XIRNKXNNONJFQO-UHFFFAOYSA-N hexadecanoic acid ethyl ester Natural products CCCCCCCCCCCCCCCC(=O)OCC XIRNKXNNONJFQO-UHFFFAOYSA-N 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N hexane carboxylic acid Natural products CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 239000002035 hexane extract Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- JXYZHMPRERWTPM-UHFFFAOYSA-N hydron;morpholine;chloride Chemical compound Cl.C1COCCN1 JXYZHMPRERWTPM-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
- 150000002691 malonic acids Chemical class 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- XEENYBWXUFATQF-UHFFFAOYSA-N methyl 2-bromoheptanoate Chemical compound CCCCCC(Br)C(=O)OC XEENYBWXUFATQF-UHFFFAOYSA-N 0.000 description 1
- QTHPWZRRQHIAHV-UHFFFAOYSA-N methyl 2-bromohexadecanoate Chemical compound CCCCCCCCCCCCCCC(Br)C(=O)OC QTHPWZRRQHIAHV-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- ZIYVHBGGAOATLY-UHFFFAOYSA-N methylmalonic acid Chemical compound OC(=O)C(C)C(O)=O ZIYVHBGGAOATLY-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N n-hexadecanoic acid Natural products CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000004767 nitrides Chemical class 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940095574 propionic acid Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- VHPSFFDJCLMFTA-UHFFFAOYSA-M sodium 6,7,8,9-tetrahydrodibenzofuran-2-thiolate Chemical compound C1=C(C=CC=2OC3=C(C21)CCCC3)[S-].[Na+] VHPSFFDJCLMFTA-UHFFFAOYSA-M 0.000 description 1
- ZXAVSKJGMIZPCH-UHFFFAOYSA-M sodium 6,7,8,9-tetrahydrodibenzofuran-3-thiolate Chemical compound C1=CC(=CC=2OC3=C(C21)CCCC3)[S-].[Na+] ZXAVSKJGMIZPCH-UHFFFAOYSA-M 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- HERSKCAGZCXYMC-UHFFFAOYSA-N thiophen-3-ol Chemical compound OC=1C=CSC=1 HERSKCAGZCXYMC-UHFFFAOYSA-N 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
- C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/76—Dibenzothiophenes
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L24/00—Arrangements for connecting or disconnecting semiconductor or solid-state bodies; Methods or apparatus related thereto
- H01L24/01—Means for bonding being attached to, or being formed on, the surface to be connected, e.g. chip-to-package, die-attach, "first-level" interconnects; Manufacturing methods related thereto
- H01L24/02—Bonding areas ; Manufacturing methods related thereto
- H01L24/04—Structure, shape, material or disposition of the bonding areas prior to the connecting process
- H01L24/05—Structure, shape, material or disposition of the bonding areas prior to the connecting process of an individual bonding area
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH425670A CH531501A (de) | 1970-03-20 | 1970-03-20 | Verfahren zur Herstellung von neuen Aryloxy- und Arylthioalkansäuren, ihren Salzen und funktionellen Derivaten |
Publications (1)
Publication Number | Publication Date |
---|---|
DE2113455A1 true DE2113455A1 (de) | 1971-10-07 |
Family
ID=4272721
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19712113455 Pending DE2113455A1 (de) | 1970-03-20 | 1971-03-19 | Verfahren zur Herstellung von neuen Aryloxy- und Arylthioalkansaeuren,ihren Salzen und funktionellen Derivaten |
Country Status (19)
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE789072A (fr) * | 1971-09-23 | 1973-03-21 | Astra Laekemedel Ab | Composes abaissant le taux de lipides du serum et leur obtention |
US3953601A (en) * | 1973-03-16 | 1976-04-27 | Aktiebolaget Astra | Dibenzothiophene derivatives as serum lipid lowering agents |
US4185108A (en) * | 1977-05-10 | 1980-01-22 | Westwood Pharmaceuticals Inc. | Antiosteoporotic agents |
US4101668A (en) * | 1977-05-10 | 1978-07-18 | Bristol-Myers Company | Antiosteoporotic agents |
US4436748A (en) | 1980-10-20 | 1984-03-13 | Hoechst-Roussel Pharmaceuticals Inc. | Benzo[b]thiophenes |
US4528399A (en) * | 1981-04-22 | 1985-07-09 | Hoechst-Roussel Pharmaceuticals Inc. | Benzo[b]thiophenes intermediates |
US4537976A (en) * | 1981-04-22 | 1985-08-27 | Hoechst-Roussel Pharmaceuticals Inc. | Benzo[b]thiophenes |
EP1100792B1 (en) * | 1998-07-30 | 2004-03-17 | Warner-Lambert Company LLC | Tricyclic sulfonamides and their derivatives as inhibitors of matrix metalloproteinases |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1997744A (en) * | 1932-10-05 | 1935-04-16 | Gen Aniline Works Inc | Hydroxydiphenylene compound |
-
1970
- 1970-03-20 CH CH1224172A patent/CH531502A/de not_active IP Right Cessation
- 1970-03-20 CH CH1223972A patent/CH530388A/de not_active IP Right Cessation
- 1970-03-20 CH CH1224072A patent/CH530389A/de not_active IP Right Cessation
- 1970-03-20 CH CH1223672A patent/CH542835A/de not_active IP Right Cessation
- 1970-03-20 CH CH425670A patent/CH531501A/de not_active IP Right Cessation
- 1970-03-20 CH CH1223872A patent/CH542837A/de not_active IP Right Cessation
- 1970-03-20 CH CH1223772A patent/CH542836A/de not_active IP Right Cessation
-
1971
- 1971-03-12 SE SE7103195A patent/SE378106B/xx unknown
- 1971-03-12 DK DK118371AA patent/DK128003B/da unknown
- 1971-03-12 NO NO956/71A patent/NO134655C/no unknown
- 1971-03-12 NL NL7103358A patent/NL7103358A/xx unknown
- 1971-03-18 ES ES389360A patent/ES389360A1/es not_active Expired
- 1971-03-18 OA OA54203A patent/OA03697A/xx unknown
- 1971-03-18 US US00125823A patent/US3784602A/en not_active Expired - Lifetime
- 1971-03-19 SU SU1688520A patent/SU419022A3/ru active
- 1971-03-19 AT AT964771A patent/AT307404B/de not_active IP Right Cessation
- 1971-03-19 AT AT964971A patent/AT307406B/de not_active IP Right Cessation
- 1971-03-19 SU SU711631737D patent/SU404258A3/ru active
- 1971-03-19 IE IE348/71A patent/IE35027B1/xx unknown
- 1971-03-19 AT AT964571A patent/AT307402B/de not_active IP Right Cessation
- 1971-03-19 FR FR7109724A patent/FR2085725B1/fr not_active Expired
- 1971-03-19 ZA ZA711800A patent/ZA711800B/xx unknown
- 1971-03-19 AT AT964671A patent/AT307403B/de not_active IP Right Cessation
- 1971-03-19 AT AT965071A patent/AT307407B/de not_active IP Right Cessation
- 1971-03-19 BE BE764536A patent/BE764536A/xx unknown
- 1971-03-19 SU SU1705729A patent/SU390716A3/ru active
- 1971-03-19 AT AT965271A patent/AT307409B/de not_active IP Right Cessation
- 1971-03-19 AT AT964871A patent/AT307405B/de not_active IP Right Cessation
- 1971-03-19 SU SU1701191A patent/SU391776A3/ru active
- 1971-03-19 AT AT239671A patent/AT302288B/de active
- 1971-03-19 DE DE19712113455 patent/DE2113455A1/de active Pending
- 1971-03-19 AT AT965171A patent/AT307408B/de not_active IP Right Cessation
- 1971-03-19 CA CA108,184A patent/CA948209A/en not_active Expired
- 1971-03-19 IL IL36447A patent/IL36447A/en unknown
- 1971-04-19 GB GB2467171*#A patent/GB1331839A/en not_active Expired
-
1972
- 1972-02-01 AR AR240319A patent/AR195372A1/es active
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