JP2008509222A

JP2008509222A - 抗菌剤

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Publication number: JP2008509222A
Authority: JP; Japan
Prior art keywords: oxo; pyrido; dihydro; methyloxy; fluoro
Prior art date: 2004-08-09
Legal status : Pending

Application number

JP2007525700A

Other languages

English (en)

Japanese (ja)

Other versions

JP2008509222A5 (enExample

Inventor

ウィリアム・ヘンリー・ミラー

マーク・アンドリュー・シーフェルド

ミーガン・ビー・ラウズ

Current Assignee

Glaxo Group Ltd

Original Assignee

Glaxo Group Ltd

Priority date

2004-08-09

Filing date

2005-08-09

Publication date

2008-03-27

2005-08-09 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

2008-03-27 Publication of JP2008509222A publication Critical patent/JP2008509222A/ja

2008-09-25 Publication of JP2008509222A5 publication Critical patent/JP2008509222A5/ja

Status Pending legal-status Critical Current

Links

239000003242 anti bacterial agent Substances 0.000 title description 4
208000035143 Bacterial infection Diseases 0.000 claims abstract description 8
241000124008 Mammalia Species 0.000 claims abstract description 8
208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 8
150000001875 compounds Chemical class 0.000 claims description 188
-1 hydroxy, amino, piperidyl Chemical group 0.000 claims description 180
229910052739 hydrogen Inorganic materials 0.000 claims description 102
239000001257 hydrogen Substances 0.000 claims description 101
125000000217 alkyl group Chemical group 0.000 claims description 94
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 67
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 66
238000002360 preparation method Methods 0.000 claims description 55
150000003839 salts Chemical class 0.000 claims description 36
125000003118 aryl group Chemical group 0.000 claims description 33
150000002431 hydrogen Chemical class 0.000 claims description 33
125000004093 cyano group Chemical group *C#N 0.000 claims description 24
125000000623 heterocyclic group Chemical group 0.000 claims description 20
238000000034 method Methods 0.000 claims description 19
229910052736 halogen Inorganic materials 0.000 claims description 18
150000002367 halogens Chemical class 0.000 claims description 18
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 18
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
125000001309 chloro group Chemical group Cl* 0.000 claims description 16
125000001153 fluoro group Chemical group F* 0.000 claims description 16
125000006574 non-aromatic ring group Chemical group 0.000 claims description 16
125000004414 alkyl thio group Chemical group 0.000 claims description 15
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 13
229910052757 nitrogen Inorganic materials 0.000 claims description 13
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 12
239000012453 solvate Substances 0.000 claims description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
125000004429 atom Chemical group 0.000 claims description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
125000002252 acyl group Chemical group 0.000 claims description 9
125000004423 acyloxy group Chemical group 0.000 claims description 9
125000003710 aryl alkyl group Chemical group 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 7
125000003277 amino group Chemical group 0.000 claims description 7
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 6
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 5
125000005035 acylthio group Chemical group 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 4
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 4
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical group C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 4
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 4
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 4
229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 4
125000005647 linker group Chemical group 0.000 claims description 4
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
GASZFYGRWPWZHP-UHFFFAOYSA-N 2h-1,4-thiazine-6-carboxamide Chemical compound NC(=O)C1=CN=CCS1 GASZFYGRWPWZHP-UHFFFAOYSA-N 0.000 claims description 3
BOUDZDHARBBOCF-UHFFFAOYSA-N 5-fluoro-n-[4-[2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperazin-1-yl]-1h-indole-2-carboxamide Chemical compound FC1=CC=C2NC(C(=O)NN3CCN(CC3)CCC3=C(F)C=NC4=CC=C(N=C43)OC)=CC2=C1 BOUDZDHARBBOCF-UHFFFAOYSA-N 0.000 claims description 3
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
239000005977 Ethylene Substances 0.000 claims description 3
125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 3
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
125000005361 aryl sulfoxide group Chemical group 0.000 claims description 3
125000005110 aryl thio group Chemical group 0.000 claims description 3
125000004104 aryloxy group Chemical group 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000005844 heterocyclyloxy group Chemical group 0.000 claims description 3
125000004468 heterocyclylthio group Chemical group 0.000 claims description 3
ASSJUZAMMDEACQ-QGZVFWFLSA-N n-[4-[(2s)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperazin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NN3CCN(CC3)C[C@@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 ASSJUZAMMDEACQ-QGZVFWFLSA-N 0.000 claims description 3
KHFMYJWGMRYIHI-UHFFFAOYSA-N n-[4-[2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]-2-(hydroxymethyl)piperazin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NN3CCN(CC3CO)CCC3=C(F)C=NC4=CC=C(N=C43)OC)=CC=C21 KHFMYJWGMRYIHI-UHFFFAOYSA-N 0.000 claims description 3
YHTHNPCOGWMJNH-UHFFFAOYSA-N n-[4-[2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]-4-hydroxypiperidin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NN3CCC(CC3)(O)CCC3=C(F)C=NC4=CC=C(N=C43)OC)=CC=C21 YHTHNPCOGWMJNH-UHFFFAOYSA-N 0.000 claims description 3
125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
KEYYINNTTKJMNJ-UHFFFAOYSA-N 2h-1,4-oxazine-6-carboxamide Chemical compound NC(=O)C1=CN=CCO1 KEYYINNTTKJMNJ-UHFFFAOYSA-N 0.000 claims description 2
241000790917 Dioxys <bee> Species 0.000 claims description 2
125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 2
125000005360 alkyl sulfoxide group Chemical group 0.000 claims description 2
150000001540 azides Chemical class 0.000 claims description 2
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 2
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
KSKGHJMVPUWETC-KBPBESRZSA-N n-[(1s,4s)-5-[2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound C1=C(OC)N=C2C(CCN3C[C@]4(N(NC(=O)C=5N=C6NC(=O)CSC6=CC=5)C[C@@]3(C4)[H])[H])=C(F)C=NC2=C1 KSKGHJMVPUWETC-KBPBESRZSA-N 0.000 claims description 2
FCZFEXYCHZTVLG-LSDHHAIUSA-N n-[(2r,5s)-4-[2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]-2,5-dimethylpiperazin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NN3[C@H](C)CN([C@H](C3)C)CCC3=C(F)C=NC4=CC=C(N=C43)OC)=CC=C21 FCZFEXYCHZTVLG-LSDHHAIUSA-N 0.000 claims description 2
MMZTYMDQGHTGFH-MRXNPFEDSA-N n-[4-[(2s)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl]piperazin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NN3CCN(CC3)C[C@@H](O)C3=C(F)C=NC4=CC=C(N=C43)OC)=CC=C21 MMZTYMDQGHTGFH-MRXNPFEDSA-N 0.000 claims description 2
BEFZENAAGJMRHC-UHFFFAOYSA-N n-[4-[2-(3-chloro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperazin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]oxazine-6-carboxamide Chemical compound O1CC(=O)NC2=NC(C(=O)NN3CCN(CC3)CCC3=C(Cl)C=NC4=CC=C(N=C43)OC)=CC=C21 BEFZENAAGJMRHC-UHFFFAOYSA-N 0.000 claims description 2
FIKIJTAROCMHCO-UHFFFAOYSA-N n-[4-[2-(3-chloro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperazin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NN3CCN(CC3)CCC3=C(Cl)C=NC4=CC=C(N=C43)OC)=CC=C21 FIKIJTAROCMHCO-UHFFFAOYSA-N 0.000 claims description 2
PYZJXNXIUWGIIO-UHFFFAOYSA-N n-[4-[2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]-1,4-diazepan-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound C12=NC(OC)=CC=C2N=CC(F)=C1CCN(CC1)CCCN1NC(=O)C1=CC=C(SCC(=O)N2)C2=N1 PYZJXNXIUWGIIO-UHFFFAOYSA-N 0.000 claims description 2
NAHBGRUGGNJCLP-UHFFFAOYSA-N n-[4-[2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperazin-1-yl]-2-(1h-indol-3-yl)-2-oxoacetamide Chemical compound C1=CC=C2C(C(=O)C(=O)NN3CCN(CC3)CCC3=C(F)C=NC4=CC=C(N=C43)OC)=CNC2=C1 NAHBGRUGGNJCLP-UHFFFAOYSA-N 0.000 claims description 2
WJZUEPVVAIYOSB-UHFFFAOYSA-N n-[4-[2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperazin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NN3CCN(CC3)CCC3=C(F)C=NC4=CC=C(N=C43)OC)=CC=C21 WJZUEPVVAIYOSB-UHFFFAOYSA-N 0.000 claims description 2
XFQCNSIBLRBCHA-UHFFFAOYSA-N n-[4-[2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperazin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NN3CCN(CC3)CCC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 XFQCNSIBLRBCHA-UHFFFAOYSA-N 0.000 claims description 2
TXGYTLAVDLFKKI-UHFFFAOYSA-N n-[4-[2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperazin-1-yl]-n-methyl-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)N(C)N3CCN(CC3)CCC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 TXGYTLAVDLFKKI-UHFFFAOYSA-N 0.000 claims description 2
HXCSKKOURLROHE-UHFFFAOYSA-N n-[4-hydroxy-4-[2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NN3CCC(CC3)(O)CCC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 HXCSKKOURLROHE-UHFFFAOYSA-N 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
125000005936 piperidyl group Chemical group 0.000 claims description 2
125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims 1
GGCDOQVRJSOLAF-UHFFFAOYSA-N 7-chloro-n-[4-[2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperazin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]oxazine-6-carboxamide Chemical compound N1C(=O)COC(C=C2Cl)=C1N=C2C(=O)NN(CC1)CCN1CCC1=C(F)C=NC2=CC=C(OC)N=C21 GGCDOQVRJSOLAF-UHFFFAOYSA-N 0.000 claims 1
MMZTYMDQGHTGFH-INIZCTEOSA-N n-[4-[(2r)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl]piperazin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NN3CCN(CC3)C[C@H](O)C3=C(F)C=NC4=CC=C(N=C43)OC)=CC=C21 MMZTYMDQGHTGFH-INIZCTEOSA-N 0.000 claims 1
DPSURABNCPDRPQ-UHFFFAOYSA-N n-[4-[2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]-2-methylpiperazin-1-yl]-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxamide Chemical compound S1CC(=O)NC2=NC(C(=O)NN3CCN(CC3C)CCC3=C(F)C=NC4=CC=C(N=C43)OC)=CC=C21 DPSURABNCPDRPQ-UHFFFAOYSA-N 0.000 claims 1
LUPYXVQFXAKNCD-UHFFFAOYSA-N n-[4-[2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperazin-1-yl]-3,4-dihydro-2h-1,5-benzodioxepine-7-carboxamide Chemical compound O1CCCOC2=CC(C(=O)NN3CCN(CC3)CCC3=C(F)C=NC4=CC=C(N=C43)OC)=CC=C21 LUPYXVQFXAKNCD-UHFFFAOYSA-N 0.000 claims 1
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 abstract 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 abstract 2
XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 abstract 2
150000005054 naphthyridines Chemical class 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 204
239000000243 solution Substances 0.000 description 161
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 124
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 80
239000007787 solid Substances 0.000 description 71
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 60
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 59
239000000203 mixture Substances 0.000 description 56
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 35
238000005481 NMR spectroscopy Methods 0.000 description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
239000000377 silicon dioxide Substances 0.000 description 32
239000000463 material Substances 0.000 description 31
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 26
230000002829 reductive effect Effects 0.000 description 25
238000006243 chemical reaction Methods 0.000 description 24
235000019439 ethyl acetate Nutrition 0.000 description 24
238000010992 reflux Methods 0.000 description 24
238000004440 column chromatography Methods 0.000 description 22
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
238000003756 stirring Methods 0.000 description 20
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
239000003921 oil Substances 0.000 description 19
235000019198 oils Nutrition 0.000 description 19
239000011734 sodium Substances 0.000 description 18
DACDXLNXHJKSJG-UHFFFAOYSA-N 8-ethenyl-2-methoxy-1,5-naphthyridine Chemical compound N1=CC=C(C=C)C2=NC(OC)=CC=C21 DACDXLNXHJKSJG-UHFFFAOYSA-N 0.000 description 17
239000000047 product Substances 0.000 description 16
238000000746 purification Methods 0.000 description 15
SZHYPQDQYNLZJP-UHFFFAOYSA-N 3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carboxylic acid Chemical compound S1CC(=O)NC2=NC(C(=O)O)=CC=C21 SZHYPQDQYNLZJP-UHFFFAOYSA-N 0.000 description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
239000002253 acid Substances 0.000 description 14
239000002904 solvent Substances 0.000 description 14
239000008346 aqueous phase Substances 0.000 description 13
XKLJHFLUAHKGGU-UHFFFAOYSA-N nitrous amide Chemical compound ON=N XKLJHFLUAHKGGU-UHFFFAOYSA-N 0.000 description 13
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 11
KWYSRDPJHYGSBD-UHFFFAOYSA-N 8-ethenyl-7-fluoro-2-methoxy-1,5-naphthyridine Chemical compound N1=CC(F)=C(C=C)C2=NC(OC)=CC=C21 KWYSRDPJHYGSBD-UHFFFAOYSA-N 0.000 description 11
125000004432 carbon atom Chemical group C* 0.000 description 11
239000000725 suspension Substances 0.000 description 11
229910052786 argon Inorganic materials 0.000 description 10
229910000027 potassium carbonate Inorganic materials 0.000 description 10
235000011181 potassium carbonates Nutrition 0.000 description 10
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 9
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
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