JP4364467B2

JP4364467B2 - ベンゾフラン誘導体、その製造法および用途

ベンゾフラン誘導体、その製造法および用途 Download PDF

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Publication number: JP4364467B2
Authority: JP; Japan
Prior art keywords: alkyl; carbonyl; aryl; atom; carbamoyl
Prior art date: 1998-12-04
Legal status : Expired - Fee Related

Application number

JP2001314027A

Other languages

English (en)

Japanese (ja)

Other versions

JP2002161088A (ja

JP2002161088A5 (enrdf_load_stackoverflow

Inventor

滋紀大川

泰由有川

浩紀加藤

政宏大倉

正記瀬藤

Current Assignee

Takeda Pharmaceutical Co Ltd

Original Assignee

Takeda Pharmaceutical Co Ltd

Priority date

1998-12-04

Filing date

2001-10-11

Publication date

2009-11-18

2001-10-11 Application filed by Takeda Pharmaceutical Co Ltd filed Critical Takeda Pharmaceutical Co Ltd

2001-10-11 Priority to JP2001314027A priority Critical patent/JP4364467B2/ja

2002-06-04 Publication of JP2002161088A publication Critical patent/JP2002161088A/ja

2005-10-13 Publication of JP2002161088A5 publication Critical patent/JP2002161088A5/ja

2009-11-18 Application granted granted Critical

2009-11-18 Publication of JP4364467B2 publication Critical patent/JP4364467B2/ja

2019-12-03 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

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238000004519 manufacturing process Methods 0.000 title claims description 7
150000001907 coumarones Chemical class 0.000 title description 2
-1 carboxy, carbamoyl Chemical group 0.000 claims description 441
125000001424 substituent group Chemical group 0.000 claims description 343
150000001875 compounds Chemical class 0.000 claims description 231
229910052757 nitrogen Inorganic materials 0.000 claims description 230
125000005842 heteroatom Chemical group 0.000 claims description 223
125000004430 oxygen atom Chemical group O* 0.000 claims description 218
229910052717 sulfur Inorganic materials 0.000 claims description 216
125000000217 alkyl group Chemical group 0.000 claims description 214
125000004433 nitrogen atom Chemical group N* 0.000 claims description 182
125000004434 sulfur atom Chemical group 0.000 claims description 177
229910052799 carbon Inorganic materials 0.000 claims description 175
125000003118 aryl group Chemical group 0.000 claims description 172
150000001721 carbon Chemical group 0.000 claims description 153
229910052736 halogen Inorganic materials 0.000 claims description 122
150000002367 halogens Chemical class 0.000 claims description 118
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 100
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 93
125000006618 5- to 10-membered aromatic heterocyclic group Chemical group 0.000 claims description 90
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 87
125000003545 alkoxy group Chemical group 0.000 claims description 75
150000003839 salts Chemical class 0.000 claims description 75
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 71
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 69
125000000623 heterocyclic group Chemical group 0.000 claims description 68
125000004432 carbon atom Chemical group C* 0.000 claims description 67
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 60
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 59
125000001769 aryl amino group Chemical group 0.000 claims description 59
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 59
125000005974 C6-C14 arylcarbonyl group Chemical group 0.000 claims description 57
125000004093 cyano group Chemical group *C#N 0.000 claims description 57
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 56
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 56
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 56
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 54
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 53
125000002252 acyl group Chemical group 0.000 claims description 52
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 52
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 51
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 51
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 48
125000005530 alkylenedioxy group Chemical group 0.000 claims description 48
125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 47
239000011593 sulfur Substances 0.000 claims description 47
125000003396 thiol group Chemical class [H]S* 0.000 claims description 47
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 45
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
229910052731 fluorine Inorganic materials 0.000 claims description 42
239000011737 fluorine Substances 0.000 claims description 40
125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 39
125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 38
125000005135 aryl sulfinyl group Chemical group 0.000 claims description 35
125000005914 C6-C14 aryloxy group Chemical group 0.000 claims description 34
125000005843 halogen group Chemical group 0.000 claims description 33
125000004442 acylamino group Chemical group 0.000 claims description 32
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 27
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 26
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 23
125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 21
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 21
230000004770 neurodegeneration Effects 0.000 claims description 20
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 19
239000003814 drug Substances 0.000 claims description 18
239000003795 chemical substances by application Substances 0.000 claims description 17
125000000753 cycloalkyl group Chemical group 0.000 claims description 17
208000024827 Alzheimer disease Diseases 0.000 claims description 16
239000003112 inhibitor Substances 0.000 claims description 16
125000004423 acyloxy group Chemical group 0.000 claims description 14
239000000203 mixture Substances 0.000 claims description 13
229940124597 therapeutic agent Drugs 0.000 claims description 13
208000018737 Parkinson disease Diseases 0.000 claims description 12
208000015122 neurodegenerative disease Diseases 0.000 claims description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
125000001153 fluoro group Chemical group F* 0.000 claims description 9
230000000508 neurotrophic effect Effects 0.000 claims description 9
HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical group C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 8
125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 8
229910052760 oxygen Chemical group 0.000 claims description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
125000000304 alkynyl group Chemical group 0.000 claims description 7
230000003449 preventive effect Effects 0.000 claims description 7
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 6
YEGLBVMYDDOCKS-UHFFFAOYSA-N 5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-3h-1-benzofuran-5-yl]-1,3-dihydroisoindole Chemical compound C1C=2C=C(OC)C(OC)=CC=2CN1C(C(=C(C)C=1OC2(C)C)C)=C(C)C=1C2C1=CC=C(C)C=C1 YEGLBVMYDDOCKS-UHFFFAOYSA-N 0.000 claims description 6
125000004104 aryloxy group Chemical group 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
150000001924 cycloalkanes Chemical class 0.000 claims description 6
239000001301 oxygen Chemical group 0.000 claims description 6
230000006974 Aβ toxicity Effects 0.000 claims description 5
125000003710 aryl alkyl group Chemical group 0.000 claims description 5
238000006467 substitution reaction Methods 0.000 claims description 5
GHNGBJQPDDWCJJ-UHFFFAOYSA-N 2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-3h-1-benzofuran-5-yl]-1,3-dihydroisoindole Chemical compound C1=CC(C)=CC=C1C1C(C)(C)OC2=C1C(C)=C(N1CC3=CC=CC=C3C1)C(C)=C2C GHNGBJQPDDWCJJ-UHFFFAOYSA-N 0.000 claims description 4
VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 4
WJVJALSWVXATEU-UHFFFAOYSA-N 6-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-3h-1-benzofuran-5-yl]-[1,3]dioxolo[4,5-f]isoindole Chemical compound C1=CC(C)=CC=C1C1C(C)(C)OC2=C1C(C)=C(N1C=C3C=C4OCOC4=CC3=C1)C(C)=C2C WJVJALSWVXATEU-UHFFFAOYSA-N 0.000 claims description 4
FDOGEKGFFDGVRV-UHFFFAOYSA-N 6-[2,2,4,6,7-pentamethyl-3-(4-propan-2-ylphenyl)-3h-1-benzofuran-5-yl]-5,7-dihydro-[1,3]dioxolo[4,5-f]isoindole Chemical compound C1=CC(C(C)C)=CC=C1C1C(C)(C)OC2=C1C(C)=C(N1CC3=CC=4OCOC=4C=C3C1)C(C)=C2C FDOGEKGFFDGVRV-UHFFFAOYSA-N 0.000 claims description 4
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
230000000069 prophylactic effect Effects 0.000 claims description 4
KYKSMISRQZMWEV-UHFFFAOYSA-N 5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-propan-2-ylphenyl)-3h-1-benzofuran-5-yl]-1,3-dihydroisoindole Chemical compound C1C=2C=C(OC)C(OC)=CC=2CN1C(C(=C(C)C=1OC2(C)C)C)=C(C)C=1C2C1=CC=C(C(C)C)C=C1 KYKSMISRQZMWEV-UHFFFAOYSA-N 0.000 claims description 3
208000026106 cerebrovascular disease Diseases 0.000 claims description 2
125000005115 alkyl carbamoyl group Chemical group 0.000 claims 58
125000005116 aryl carbamoyl group Chemical group 0.000 claims 29
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims 28
125000005199 aryl carbonyloxy group Chemical group 0.000 claims 28
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims 27
125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims 27
125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims 25
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims 20
125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims 12
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 11
125000005596 alkyl carboxamido group Chemical group 0.000 claims 11
125000004429 atom Chemical group 0.000 claims 11
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims 10
125000005915 C6-C14 aryl group Chemical group 0.000 claims 8
125000005431 alkyl carboxamide group Chemical group 0.000 claims 7
125000004070 6 membered heterocyclic group Chemical group 0.000 claims 5
125000004658 aryl carbonyl amino group Chemical group 0.000 claims 5
125000004644 alkyl sulfinyl group Chemical group 0.000 claims 4
125000005251 aryl acyl group Chemical group 0.000 claims 3
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 3
125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims 3
GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims 3
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 3
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 3
LWTJKYLZMBZIJB-UHFFFAOYSA-N 2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-3h-1-benzofuran Chemical compound C1=CC(C)=CC=C1C1C(C)(C)OC2=C1C(C)=CC(C)=C2C LWTJKYLZMBZIJB-UHFFFAOYSA-N 0.000 claims 2
241000255925 Diptera Species 0.000 claims 2
125000004390 alkyl sulfonyl group Chemical group 0.000 claims 2
150000001555 benzenes Chemical group 0.000 claims 1
125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 claims 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
238000006243 chemical reaction Methods 0.000 description 114
150000002430 hydrocarbons Chemical group 0.000 description 71
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 58
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
239000002904 solvent Substances 0.000 description 45
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
239000002585 base Substances 0.000 description 34
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 34
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 32
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 31
239000000460 chlorine Substances 0.000 description 28
229910052801 chlorine Inorganic materials 0.000 description 28
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 26
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
229930195733 hydrocarbon Natural products 0.000 description 26
238000000034 method Methods 0.000 description 25
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
229910052794 bromium Inorganic materials 0.000 description 24
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 23
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 23
150000001408 amides Chemical class 0.000 description 20
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 20
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
125000001931 aliphatic group Chemical group 0.000 description 19
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 19
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 18
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 18
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 16
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 16
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
150000002170 ethers Chemical class 0.000 description 16
150000008282 halocarbons Chemical class 0.000 description 16
239000012046 mixed solvent Substances 0.000 description 16
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 16
230000035484 reaction time Effects 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
125000004414 alkyl thio group Chemical group 0.000 description 15
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 14
238000004587 chromatography analysis Methods 0.000 description 14
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 14
238000001953 recrystallisation Methods 0.000 description 14
238000000926 separation method Methods 0.000 description 14
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
239000003377 acid catalyst Substances 0.000 description 13
150000001298 alcohols Chemical class 0.000 description 13
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 13
238000007796 conventional method Methods 0.000 description 13
238000004821 distillation Methods 0.000 description 13
229910052751 metal Inorganic materials 0.000 description 13
239000002184 metal Substances 0.000 description 13
239000000047 product Substances 0.000 description 13
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 13
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
150000003462 sulfoxides Chemical class 0.000 description 13
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 12
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
230000009471 action Effects 0.000 description 12
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 12
125000005279 aryl sulfonyloxy group Chemical group 0.000 description 12
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 12
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 12
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 12
239000000243 solution Substances 0.000 description 12
102000013455 Amyloid beta-Peptides Human genes 0.000 description 11
108010090849 Amyloid beta-Peptides Proteins 0.000 description 11
239000004215 Carbon black (E152) Substances 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
239000002253 acid Substances 0.000 description 11
150000001447 alkali salts Chemical class 0.000 description 11
125000003342 alkenyl group Chemical group 0.000 description 11
239000012043 crude product Substances 0.000 description 11
108010025020 Nerve Growth Factor Proteins 0.000 description 10
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 10
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 10
230000002401 inhibitory effect Effects 0.000 description 10
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 9
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 9
239000002841 Lewis acid Substances 0.000 description 9
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 9
HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 9
150000007517 lewis acids Chemical class 0.000 description 9
125000001544 thienyl group Chemical group 0.000 description 9
239000008096 xylene Substances 0.000 description 9
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 8
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 8
102000007072 Nerve Growth Factors Human genes 0.000 description 8
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