TW201745B

TW201745B -

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Publication number: TW201745B
Authority: TW; Taiwan
Prior art keywords: methyl; bromo; benzofuranyl; imidazole; group
Prior art date: 1989-12-01

Application number

TW79110222A

Other languages

English (en)

Chinese (zh)

Inventor

Dennis Dowle Michael

Original Assignee

Glaxo Group Ltd

Priority date

1989-12-01

Filing date

1990-12-04

Publication date

1993-03-11

1989-12-01 Priority claimed from GB898927277A external-priority patent/GB8927277D0/en

1989-12-22 Priority claimed from GB898929071A external-priority patent/GB8929071D0/en

1990-09-06 Priority claimed from GB909019436A external-priority patent/GB9019436D0/en

1990-12-04 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1993-03-11 Application granted granted Critical

1993-03-11 Publication of TW201745B publication Critical patent/TW201745B/zh

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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 401
150000001875 compounds Chemical class 0.000 claims description 354
XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 330
239000000243 solution Substances 0.000 claims description 311
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 282
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 193
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 161
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 159
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 103
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 96
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 88
238000011049 filling Methods 0.000 claims description 81
239000002904 solvent Substances 0.000 claims description 79
-1 alkoxycarbonyloxyalkyl ester Chemical class 0.000 claims description 77
238000000034 method Methods 0.000 claims description 72
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 70
229910052757 nitrogen Inorganic materials 0.000 claims description 52
125000000217 alkyl group Chemical group 0.000 claims description 43
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 41
239000002253 acid Substances 0.000 claims description 37
238000006243 chemical reaction Methods 0.000 claims description 37
238000004440 column chromatography Methods 0.000 claims description 37
150000002148 esters Chemical class 0.000 claims description 37
150000003839 salts Chemical class 0.000 claims description 34
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 33
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 32
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 31
240000004808 Saccharomyces cerevisiae Species 0.000 claims description 26
239000007788 liquid Substances 0.000 claims description 25
125000005843 halogen group Chemical group 0.000 claims description 24
238000007639 printing Methods 0.000 claims description 24
239000012453 solvate Substances 0.000 claims description 23
239000007789 gas Substances 0.000 claims description 19
238000004364 calculation method Methods 0.000 claims description 16
238000001035 drying Methods 0.000 claims description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
125000003545 alkoxy group Chemical group 0.000 claims description 15
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 14
229910000041 hydrogen chloride Inorganic materials 0.000 claims description 14
238000012360 testing method Methods 0.000 claims description 14
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 14
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 13
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
125000003342 alkenyl group Chemical group 0.000 claims description 12
238000004458 analytical method Methods 0.000 claims description 12
125000004429 atom Chemical group 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
229910052786 argon Inorganic materials 0.000 claims description 11
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 11
238000006467 substitution reaction Methods 0.000 claims description 11
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 10
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
150000001412 amines Chemical class 0.000 claims description 10
125000004494 ethyl ester group Chemical group 0.000 claims description 10
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 10
125000006239 protecting group Chemical group 0.000 claims description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 9
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
235000021419 vinegar Nutrition 0.000 claims description 9
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
125000002883 imidazolyl group Chemical group 0.000 claims description 8
239000000126 substance Substances 0.000 claims description 8
239000003795 chemical substances by application Substances 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
125000001153 fluoro group Chemical group F* 0.000 claims description 7
108090000765 processed proteins & peptides Proteins 0.000 claims description 7
102000004190 Enzymes Human genes 0.000 claims description 6
108090000790 Enzymes Proteins 0.000 claims description 6
125000005907 alkyl ester group Chemical group 0.000 claims description 6
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
150000003254 radicals Chemical group 0.000 claims description 6
150000001335 aliphatic alkanes Chemical class 0.000 claims description 5
125000003277 amino group Chemical group 0.000 claims description 5
150000001540 azides Chemical class 0.000 claims description 5
150000004677 hydrates Chemical class 0.000 claims description 5
230000002503 metabolic effect Effects 0.000 claims description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
239000011780 sodium chloride Substances 0.000 claims description 5
206010019280 Heart failures Diseases 0.000 claims description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
125000002541 furyl group Chemical group 0.000 claims description 4
GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 4
150000004682 monohydrates Chemical class 0.000 claims description 4
230000002265 prevention Effects 0.000 claims description 4
150000003536 tetrazoles Chemical group 0.000 claims description 4
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims description 3
125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 claims description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
229940079593 drug Drugs 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
235000019253 formic acid Nutrition 0.000 claims description 3
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 3
230000004060 metabolic process Effects 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical group NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 2
208000010412 Glaucoma Diseases 0.000 claims description 2
208000001647 Renal Insufficiency Diseases 0.000 claims description 2
230000005856 abnormality Effects 0.000 claims description 2
125000005997 bromomethyl group Chemical group 0.000 claims description 2
125000002843 carboxylic acid group Chemical group 0.000 claims description 2
KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical class [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 claims description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
239000012530 fluid Substances 0.000 claims description 2
230000005764 inhibitory process Effects 0.000 claims description 2
201000006370 kidney failure Diseases 0.000 claims description 2
208000010125 myocardial infarction Diseases 0.000 claims description 2
239000003973 paint Substances 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
238000000926 separation method Methods 0.000 claims description 2
125000004183 alkoxy alkyl group Chemical group 0.000 claims 5
230000004580 weight loss Effects 0.000 claims 5
108010064733 Angiotensins Proteins 0.000 claims 2
102000015427 Angiotensins Human genes 0.000 claims 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims 2
229920002873 Polyethylenimine Polymers 0.000 claims 2
125000005605 benzo group Chemical group 0.000 claims 2
239000007853 buffer solution Substances 0.000 claims 2
239000013078 crystal Substances 0.000 claims 2
238000010586 diagram Methods 0.000 claims 2
125000002768 hydroxyalkyl group Chemical group 0.000 claims 2
210000004185 liver Anatomy 0.000 claims 2
238000012856 packing Methods 0.000 claims 2
FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 claims 2
238000000159 protein binding assay Methods 0.000 claims 2
239000002287 radioligand Substances 0.000 claims 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 2
238000010998 test method Methods 0.000 claims 2
YXMWGHKZTMANIJ-UHFFFAOYSA-N 1h-pyrrol-2-ylmethanamine Chemical compound NCC1=CC=CN1 YXMWGHKZTMANIJ-UHFFFAOYSA-N 0.000 claims 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 claims 1
NRGGMCIBEHEAIL-UHFFFAOYSA-N 2-ethylpyridine Chemical compound CCC1=CC=CC=N1 NRGGMCIBEHEAIL-UHFFFAOYSA-N 0.000 claims 1
SYPGLBQMKKIYJE-UHFFFAOYSA-N 3-[[3-bromo-2-[2-(2h-tetrazol-5-yl)phenyl]-1-benzofuran-5-yl]methyl]-2-butyl-5-iodoimidazole-4-carboxylic acid Chemical compound CCCCC1=NC(I)=C(C(O)=O)N1CC1=CC=C(OC(=C2Br)C=3C(=CC=CC=3)C3=NNN=N3)C2=C1 SYPGLBQMKKIYJE-UHFFFAOYSA-N 0.000 claims 1
MCPCYOKEYHLOSZ-UHFFFAOYSA-N 3-[[3-bromo-2-[2-(trifluoromethylsulfonylamino)phenyl]-1-benzofuran-5-yl]methyl]-2-butyl-5-chloroimidazole-4-carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=C(OC(=C2Br)C=3C(=CC=CC=3)NS(=O)(=O)C(F)(F)F)C2=C1 MCPCYOKEYHLOSZ-UHFFFAOYSA-N 0.000 claims 1
101800000734 Angiotensin-1 Proteins 0.000 claims 1
102400000344 Angiotensin-1 Human genes 0.000 claims 1
KFZSNJIFZRMWBP-UHFFFAOYSA-N C(C)C1=NC=CC=C1.[O] Chemical compound C(C)C1=NC=CC=C1.[O] KFZSNJIFZRMWBP-UHFFFAOYSA-N 0.000 claims 1
206010007559 Cardiac failure congestive Diseases 0.000 claims 1
101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims 1
241000255925 Diptera Species 0.000 claims 1
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 1
206010020571 Hyperaldosteronism Diseases 0.000 claims 1
239000004677 Nylon Substances 0.000 claims 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
DQJKDFOOHKXTKN-UHFFFAOYSA-N [3-[[3-bromo-2-[2-(2h-tetrazol-5-yl)phenyl]-1-benzofuran-5-yl]methyl]-2-butyl-5-chloroimidazol-4-yl]methanol Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(OC(=C2Br)C=3C(=CC=CC=3)C=3NN=NN=3)C2=C1 DQJKDFOOHKXTKN-UHFFFAOYSA-N 0.000 claims 1
ITBPIKUGMIZTJR-UHFFFAOYSA-N [bis(hydroxymethyl)amino]methanol Chemical compound OCN(CO)CO ITBPIKUGMIZTJR-UHFFFAOYSA-N 0.000 claims 1
238000010521 absorption reaction Methods 0.000 claims 1
125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims 1
125000005205 alkoxycarbonyloxyalkyl group Chemical group 0.000 claims 1
125000004103 aminoalkyl group Chemical group 0.000 claims 1
125000005127 aryl alkoxy alkyl group Chemical group 0.000 claims 1
125000005160 aryl oxy alkyl group Chemical group 0.000 claims 1
SOMSXRFNBORXAU-UHFFFAOYSA-N benzene toluene Chemical compound C1=CC=CC=C1.CC1=CC=CC=C1.CC1=CC=CC=C1 SOMSXRFNBORXAU-UHFFFAOYSA-N 0.000 claims 1
239000008280 blood Substances 0.000 claims 1
210000004369 blood Anatomy 0.000 claims 1
230000001149 cognitive effect Effects 0.000 claims 1
239000012153 distilled water Substances 0.000 claims 1
MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 claims 1
238000002474 experimental method Methods 0.000 claims 1
238000004880 explosion Methods 0.000 claims 1
UTVVREMVDJTZAC-UHFFFAOYSA-N furan-2-amine Chemical compound NC1=CC=CO1 UTVVREMVDJTZAC-UHFFFAOYSA-N 0.000 claims 1
239000003365 glass fiber Substances 0.000 claims 1
238000000265 homogenisation Methods 0.000 claims 1
239000011539 homogenization buffer Substances 0.000 claims 1
238000002329 infrared spectrum Methods 0.000 claims 1
230000002401 inhibitory effect Effects 0.000 claims 1
239000003446 ligand Substances 0.000 claims 1
239000000155 melt Substances 0.000 claims 1
150000004767 nitrides Chemical class 0.000 claims 1
229920001778 nylon Polymers 0.000 claims 1
230000035479 physiological effects, processes and functions Effects 0.000 claims 1
239000004033 plastic Substances 0.000 claims 1
229920003023 plastic Polymers 0.000 claims 1
239000001294 propane Substances 0.000 claims 1
238000001525 receptor binding assay Methods 0.000 claims 1
102000005962 receptors Human genes 0.000 claims 1
108020003175 receptors Proteins 0.000 claims 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 claims 1
239000001384 succinic acid Substances 0.000 claims 1
229910052717 sulfur Inorganic materials 0.000 claims 1
239000011593 sulfur Substances 0.000 claims 1
239000013589 supplement Substances 0.000 claims 1
208000011580 syndromic disease Diseases 0.000 claims 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims 1
238000003828 vacuum filtration Methods 0.000 claims 1
230000002792 vascular Effects 0.000 claims 1
239000000543 intermediate Substances 0.000 description 398
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 243
239000000203 mixture Substances 0.000 description 183
239000007787 solid Substances 0.000 description 168
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 148
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 123
229940093499 ethyl acetate Drugs 0.000 description 111
238000003756 stirring Methods 0.000 description 98
239000000284 extract Substances 0.000 description 95
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 74
239000006260 foam Substances 0.000 description 70
230000008018 melting Effects 0.000 description 70
238000002844 melting Methods 0.000 description 70
238000004587 chromatography analysis Methods 0.000 description 64
235000019441 ethanol Nutrition 0.000 description 57
239000003921 oil Substances 0.000 description 56
235000019198 oils Nutrition 0.000 description 56
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 54
239000003208 petroleum Substances 0.000 description 47
238000010992 reflux Methods 0.000 description 46
239000000843 powder Substances 0.000 description 43
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
239000011541 reaction mixture Substances 0.000 description 42
239000002585 base Substances 0.000 description 39
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 39
BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 34
239000000725 suspension Substances 0.000 description 34
VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 33
239000000047 product Substances 0.000 description 33
229960000583 acetic acid Drugs 0.000 description 31
239000007864 aqueous solution Substances 0.000 description 29
239000010410 layer Substances 0.000 description 27
229910000027 potassium carbonate Inorganic materials 0.000 description 27
239000008346 aqueous phase Substances 0.000 description 26
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 22
239000012267 brine Substances 0.000 description 22
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 20
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
239000012074 organic phase Substances 0.000 description 19
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 18
235000013405 beer Nutrition 0.000 description 18
238000001704 evaporation Methods 0.000 description 17
238000011161 development Methods 0.000 description 16
238000000746 purification Methods 0.000 description 16
208000004350 Strabismus Diseases 0.000 description 15
238000001914 filtration Methods 0.000 description 15
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
239000012071 phase Substances 0.000 description 14
229910052704 radon Inorganic materials 0.000 description 14
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 13
235000008504 concentrate Nutrition 0.000 description 13
239000012141 concentrate Substances 0.000 description 13
230000008020 evaporation Effects 0.000 description 13
239000011734 sodium Substances 0.000 description 13
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
239000005526 vasoconstrictor agent Substances 0.000 description 13
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
238000010438 heat treatment Methods 0.000 description 12
238000004898 kneading Methods 0.000 description 12
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 12
238000012795 verification Methods 0.000 description 12
101800001386 Peptide II Proteins 0.000 description 11
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
238000001816 cooling Methods 0.000 description 11
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 11
229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 11
229910052794 bromium Inorganic materials 0.000 description 10
238000007667 floating Methods 0.000 description 10
239000000463 material Substances 0.000 description 10
239000002244 precipitate Substances 0.000 description 10
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 9
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000000354 decomposition reaction Methods 0.000 description 9
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125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
125000005207 tetraalkylammonium group Chemical group 0.000 description 1
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WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
239000010937 tungsten Substances 0.000 description 1
238000007039 two-step reaction Methods 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
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238000010792 warming Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000002759 woven fabric Substances 0.000 description 1
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