JPH0219837B2

JPH0219837B2 -

Info

Publication number: JPH0219837B2
Authority: JP; Japan
Prior art keywords: thiophene; sulfamoylbenzo; hydroxy; formula; alkyl
Prior art date: 1983-06-20
Legal status : Expired

Application number

JP12545484A

Other languages

English (en)

Japanese (ja)

Other versions

JPS6036481A (ja

Inventor

Eru Shepaado Kenesu

Eru Kurahamu Samyueru

Current Assignee

Merck and Co Inc

Original Assignee

Merck and Co Inc

Priority date

1983-06-20

Filing date

1984-06-20

Publication date

1990-05-07

1984-06-20 Application filed by Merck and Co Inc filed Critical Merck and Co Inc

1985-02-25 Publication of JPS6036481A publication Critical patent/JPS6036481A/ja

1990-05-07 Publication of JPH0219837B2 publication Critical patent/JPH0219837B2/ja

Status Granted legal-status Critical Current

Links

YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 233
229930192474 thiophene Natural products 0.000 claims description 119
-1 oxazolidylmethyloxy Chemical group 0.000 claims description 69
125000001544 thienyl group Chemical group 0.000 claims description 41
150000001875 compounds Chemical class 0.000 claims description 40
239000011734 sodium Substances 0.000 claims description 29
125000000217 alkyl group Chemical group 0.000 claims description 21
229910052739 hydrogen Inorganic materials 0.000 claims description 18
239000001257 hydrogen Substances 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 16
125000001475 halogen functional group Chemical group 0.000 claims description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
125000002947 alkylene group Chemical group 0.000 claims description 11
238000011282 treatment Methods 0.000 claims description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 8
125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
XRZYWSVMYHEQPN-UHFFFAOYSA-N 6-hydroxy-1-benzothiophene-2-sulfonamide Chemical compound C1=C(O)C=C2SC(S(=O)(=O)N)=CC2=C1 XRZYWSVMYHEQPN-UHFFFAOYSA-N 0.000 claims description 4
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 3
JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 claims description 3
KQNPFQTWMSNSAP-UHFFFAOYSA-M isobutyrate Chemical compound CC(C)C([O-])=O KQNPFQTWMSNSAP-UHFFFAOYSA-M 0.000 claims description 3
JDRMYOQETPMYQX-UHFFFAOYSA-N monomethyl succinate Chemical compound COC(=O)CCC(O)=O JDRMYOQETPMYQX-UHFFFAOYSA-N 0.000 claims description 3
235000019157 thiamine Nutrition 0.000 claims description 3
KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 claims description 3
229960003495 thiamine Drugs 0.000 claims description 3
239000011721 thiamine Substances 0.000 claims description 3
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 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
229910021529 ammonia Inorganic materials 0.000 claims description 2
229940077388 benzenesulfonate Drugs 0.000 claims description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 2
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
125000005475 oxolanyl group Chemical group 0.000 claims description 2
JBKPUQTUERUYQE-UHFFFAOYSA-O pralidoxime Chemical compound C[N+]1=CC=CC=C1\C=N\O JBKPUQTUERUYQE-UHFFFAOYSA-O 0.000 claims description 2
229960003370 pralidoxime Drugs 0.000 claims description 2
229910052708 sodium Inorganic materials 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 18
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 2
RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical compound C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 claims 1
QPFYXYFORQJZEC-FOCLMDBBSA-N Phenazopyridine Chemical compound NC1=NC(N)=CC=C1\N=N\C1=CC=CC=C1 QPFYXYFORQJZEC-FOCLMDBBSA-N 0.000 claims 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
150000001768 cations Chemical class 0.000 claims 1
230000003301 hydrolyzing effect Effects 0.000 claims 1
229910052700 potassium Inorganic materials 0.000 claims 1
239000011591 potassium Substances 0.000 claims 1
229940070891 pyridium Drugs 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 168
239000000243 solution Substances 0.000 description 106
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 104
239000000203 mixture Substances 0.000 description 94
239000007787 solid Substances 0.000 description 87
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
239000000047 product Substances 0.000 description 76
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 69
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
238000002360 preparation method Methods 0.000 description 45
239000002904 solvent Substances 0.000 description 45
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 31
239000011541 reaction mixture Substances 0.000 description 31
238000006243 chemical reaction Methods 0.000 description 30
238000003756 stirring Methods 0.000 description 30
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 29
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
238000004458 analytical method Methods 0.000 description 28
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
239000000284 extract Substances 0.000 description 27
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
238000000034 method Methods 0.000 description 26
238000001953 recrystallisation Methods 0.000 description 26
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
230000002829 reductive effect Effects 0.000 description 21
238000010992 reflux Methods 0.000 description 20
239000000725 suspension Substances 0.000 description 20
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 15
239000010410 layer Substances 0.000 description 15
235000002639 sodium chloride Nutrition 0.000 description 15
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 14
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 12
239000012267 brine Substances 0.000 description 12
239000003610 charcoal Substances 0.000 description 12
229940079593 drug Drugs 0.000 description 12
239000003814 drug Substances 0.000 description 12
239000000463 material Substances 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
239000012043 crude product Substances 0.000 description 11
239000003921 oil Substances 0.000 description 11
235000019198 oils Nutrition 0.000 description 11
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
239000007788 liquid Substances 0.000 description 10
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 10
239000000741 silica gel Substances 0.000 description 10
229910002027 silica gel Inorganic materials 0.000 description 10
UZMQSZBTFGHLAH-UHFFFAOYSA-N 1-benzothiophene-2-sulfonamide Chemical compound C1=CC=C2SC(S(=O)(=O)N)=CC2=C1 UZMQSZBTFGHLAH-UHFFFAOYSA-N 0.000 description 9
BKBZFJRHYSCZQA-UHFFFAOYSA-N 2-methoxy-2-methylpropanoic acid Chemical compound COC(C)(C)C(O)=O BKBZFJRHYSCZQA-UHFFFAOYSA-N 0.000 description 9
PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical class NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
238000007792 addition Methods 0.000 description 9
239000000538 analytical sample Substances 0.000 description 9
239000003795 chemical substances by application Substances 0.000 description 9
238000001035 drying Methods 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
229910052757 nitrogen Inorganic materials 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
CHXZRHMQQRUVHF-UHFFFAOYSA-N 2-hex-5-en-1,3-diynyl-5-prop-1-ynylthiophene Chemical compound CC#CC1=CC=C(C#CC#CC=C)S1 CHXZRHMQQRUVHF-UHFFFAOYSA-N 0.000 description 8
WGDVDMKNSDCNGB-UHFFFAOYSA-N 6-methoxy-1-benzothiophene Chemical compound COC1=CC=C2C=CSC2=C1 WGDVDMKNSDCNGB-UHFFFAOYSA-N 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
238000001816 cooling Methods 0.000 description 8
238000001914 filtration Methods 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
208000010412 Glaucoma Diseases 0.000 description 7
229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 7
239000003489 carbonate dehydratase inhibitor Substances 0.000 description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
238000009835 boiling Methods 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
238000002425 crystallisation Methods 0.000 description 6
230000008025 crystallization Effects 0.000 description 6
230000004406 elevated intraocular pressure Effects 0.000 description 6
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
230000004410 intraocular pressure Effects 0.000 description 6
238000002844 melting Methods 0.000 description 6
230000008018 melting Effects 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 6
239000012258 stirred mixture Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
238000005406 washing Methods 0.000 description 6
JRTUPGWOWBPJAF-UHFFFAOYSA-N 3-hydroxy-1-benzothiophene-2-sulfonamide Chemical compound C1=CC=C2C(O)=C(S(=O)(=O)N)SC2=C1 JRTUPGWOWBPJAF-UHFFFAOYSA-N 0.000 description 5
102000003846 Carbonic anhydrases Human genes 0.000 description 5
108090000209 Carbonic anhydrases Proteins 0.000 description 5
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 5
239000007832 Na2SO4 Substances 0.000 description 5
235000011114 ammonium hydroxide Nutrition 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
239000000969 carrier Substances 0.000 description 5
239000012141 concentrate Substances 0.000 description 5
239000013078 crystal Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000002024 ethyl acetate extract Substances 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
239000005457 ice water Substances 0.000 description 5
238000004519 manufacturing process Methods 0.000 description 5
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 5
239000008194 pharmaceutical composition Substances 0.000 description 5
235000011181 potassium carbonates Nutrition 0.000 description 5
239000000843 powder Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000012047 saturated solution Substances 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
239000000126 substance Substances 0.000 description 5
WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
IGYDWQWQYFXSNN-UHFFFAOYSA-N 5-hydroxy-1-benzothiophene-2-sulfonamide Chemical compound OC1=CC=C2SC(S(=O)(=O)N)=CC2=C1 IGYDWQWQYFXSNN-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
239000012346 acetyl chloride Substances 0.000 description 4
239000002585 base Substances 0.000 description 4
239000002876 beta blocker Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
238000000354 decomposition reaction Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000009472 formulation Methods 0.000 description 4
239000007789 gas Substances 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
230000007246 mechanism Effects 0.000 description 4
239000000155 melt Substances 0.000 description 4
235000017281 sodium acetate Nutrition 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
229940124530 sulfonamide Drugs 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 3
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
WXRMVOSEIGZNPW-UHFFFAOYSA-N 3-amino-1-benzothiophene-2-sulfonamide Chemical compound NC=1C2=C(SC=1S(N)(=O)=O)C=CC=C2 WXRMVOSEIGZNPW-UHFFFAOYSA-N 0.000 description 3
QMVAZEHZOPDGHA-UHFFFAOYSA-N 3-methoxybenzenethiol Chemical compound COC1=CC=CC(S)=C1 QMVAZEHZOPDGHA-UHFFFAOYSA-N 0.000 description 3
UBAJGSNHCORLER-UHFFFAOYSA-N 5-(methoxymethyl)-1-benzothiophene-2-sulfonamide Chemical compound COCC1=CC=C2SC(S(N)(=O)=O)=CC2=C1 UBAJGSNHCORLER-UHFFFAOYSA-N 0.000 description 3
RDSIMGKJEYNNLF-UHFFFAOYSA-N 5-bromo-1-benzothiophene Chemical compound BrC1=CC=C2SC=CC2=C1 RDSIMGKJEYNNLF-UHFFFAOYSA-N 0.000 description 3
PNLRJPAUMHTMEL-UHFFFAOYSA-N 7-hydroxy-1-benzothiophene-2-sulfonamide Chemical compound C1=CC(O)=C2SC(S(=O)(=O)N)=CC2=C1 PNLRJPAUMHTMEL-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
229910019142 PO4 Inorganic materials 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
150000003863 ammonium salts Chemical class 0.000 description 3
MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 3
LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 3
230000006378 damage Effects 0.000 description 3
238000010828 elution Methods 0.000 description 3
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