KR102239725B1 - 디아자비시클로옥탄 유도체의 제조법과 그의 중간체 - Google Patents

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Publication number

KR102239725B1

KR102239725B1 KR1020167009769A KR20167009769A KR102239725B1 KR 102239725 B1 KR102239725 B1 KR 102239725B1 KR 1020167009769 A KR1020167009769 A KR 1020167009769A KR 20167009769 A KR20167009769 A KR 20167009769A KR 102239725 B1 KR102239725 B1 KR 102239725B1

Authority

KR

South Korea

Prior art keywords

benzyloxy

tert

amino

compound represented

added

Prior art date

2013-09-24

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.)

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• 238000004519 manufacturing process Methods 0.000 title claims abstract description 54
• NFDXQGNDWIPXQL-UHFFFAOYSA-N 1-cyclooctyldiazocane Chemical class C1CCCCCCC1N1NCCCCCC1 NFDXQGNDWIPXQL-UHFFFAOYSA-N 0.000 title abstract description 6
• -1 2,5-dioxopyrrolidin-1-yl Chemical group 0.000 claims abstract description 279
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 29
• 125000006239 protecting group Chemical group 0.000 claims abstract description 28
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 21
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 21
• 239000001257 hydrogen Substances 0.000 claims abstract description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
• 150000001875 compounds Chemical class 0.000 claims description 460
• 238000006243 chemical reaction Methods 0.000 claims description 119
• 238000000034 method Methods 0.000 claims description 109
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 44
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 20
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 19
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 18
• 239000002253 acid Substances 0.000 claims description 15
• 239000003795 chemical substances by application Substances 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 claims description 11
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 10
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 10
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical group ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 9
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• GNJKALOITRXADZ-UHFFFAOYSA-N 2-hydroxy-3a,4,7,7a-tetrahydroisoindole-1,3-dione Chemical compound C1C=CCC2C(=O)N(O)C(=O)C21 GNJKALOITRXADZ-UHFFFAOYSA-N 0.000 claims description 6
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 5
• DBWVTDFTWIVIQA-UHFFFAOYSA-N 2-hydroxy-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound C1CCCC2C(=O)N(O)C(=O)C21 DBWVTDFTWIVIQA-UHFFFAOYSA-N 0.000 claims description 5
• ZUSSTQCWRDLYJA-UHFFFAOYSA-N n-hydroxy-5-norbornene-2,3-dicarboximide Chemical compound C1=CC2CC1C1C2C(=O)N(O)C1=O ZUSSTQCWRDLYJA-UHFFFAOYSA-N 0.000 claims description 5
• 125000004122 cyclic group Chemical group 0.000 claims description 4
• XZLRJCSXDLXBSC-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl 2-cyanoacetate Chemical group CC(C)(C)OC(=O)NCCCOC(=O)CC#N XZLRJCSXDLXBSC-UHFFFAOYSA-N 0.000 claims description 2
• 125000005842 heteroatom Chemical group 0.000 claims description 2
• KRZJRNZICWNMOA-GXSJLCMTSA-N (3s,4r)-4,8-dihydroxy-3-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1=CC=C2[C@@H](O)[C@@H](OC)CC(=O)C2=C1O KRZJRNZICWNMOA-GXSJLCMTSA-N 0.000 claims 2
• 125000001072 heteroaryl group Chemical group 0.000 claims 1
• 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 695
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 346
• 239000000243 solution Substances 0.000 description 254
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 232
• 239000000203 mixture Substances 0.000 description 193
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 165
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 117
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 114
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 99
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 98
• 230000008569 process Effects 0.000 description 95
• 238000003756 stirring Methods 0.000 description 93
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 92
• 238000010898 silica gel chromatography Methods 0.000 description 92
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 91
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 89
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 88
• 238000000746 purification Methods 0.000 description 73
• 238000002955 isolation Methods 0.000 description 62
• 238000001816 cooling Methods 0.000 description 60
• 239000002904 solvent Substances 0.000 description 59
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 57
• 229960004106 citric acid Drugs 0.000 description 55
• 239000012044 organic layer Substances 0.000 description 47
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
• FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 45
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 42
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 41
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 40
• 239000010410 layer Substances 0.000 description 40
• OTCZPAORUHCZJC-CABCVRRESA-N (2s,5r)-1-[(2-methylpropan-2-yl)oxycarbonyl]-5-(phenylmethoxyamino)piperidine-2-carboxylic acid Chemical compound C1C[C@@H](C(O)=O)N(C(=O)OC(C)(C)C)C[C@@H]1NOCC1=CC=CC=C1 OTCZPAORUHCZJC-CABCVRRESA-N 0.000 description 39
• 239000011736 potassium bicarbonate Substances 0.000 description 39
• 235000015497 potassium bicarbonate Nutrition 0.000 description 39
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 39
• 229940086066 potassium hydrogencarbonate Drugs 0.000 description 39
• 229940098779 methanesulfonic acid Drugs 0.000 description 38
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
• UMHGLONVYIYIOU-NEPJUHHUSA-N (2s,5r)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid Chemical compound C([C@]1(CC[C@H]2C(O)=O)[H])N2C(=O)N1OCC1=CC=CC=C1 UMHGLONVYIYIOU-NEPJUHHUSA-N 0.000 description 26
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 26
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 25
• XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 24
• 239000007787 solid Substances 0.000 description 22
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 20
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
• JRLJOAREDJOYLW-UHFFFAOYSA-N tert-butyl n-(2-aminooxyethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCON JRLJOAREDJOYLW-UHFFFAOYSA-N 0.000 description 19
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
• 239000007864 aqueous solution Substances 0.000 description 16
• 239000000706 filtrate Substances 0.000 description 15
• HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 15
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 14
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
• 239000013078 crystal Substances 0.000 description 13
• QUOAQASBSYHDJY-OLZOCXBDSA-N methyl (2s,5r)-5-(phenylmethoxyamino)piperidine-2-carboxylate Chemical compound C1N[C@H](C(=O)OC)CC[C@H]1NOCC1=CC=CC=C1 QUOAQASBSYHDJY-OLZOCXBDSA-N 0.000 description 13
• YJJUEXDKLHCGEM-OLZOCXBDSA-N methyl (2s,5r)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carboxylate Chemical compound C([C@]1(CC[C@H]2C(=O)OC)[H])N2C(=O)N1OCC1=CC=CC=C1 YJJUEXDKLHCGEM-OLZOCXBDSA-N 0.000 description 13
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 12
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
• 230000018044 dehydration Effects 0.000 description 12
• 238000006297 dehydration reaction Methods 0.000 description 12
• 238000004128 high performance liquid chromatography Methods 0.000 description 12
• 239000011541 reaction mixture Substances 0.000 description 12
• 125000004079 stearyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
• DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 12
• UZPRANDKHUQWBS-SVHRXORXSA-N (2S,5R)-2-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid Chemical compound C1C[C@](N2C[C@@H]1N(C2=O)OCC3=CC=CC=C3)(C(=O)O)N4C(=O)[C@H]5[C@@H]6C[C@H]([C@H]5C4=O)C=C6 UZPRANDKHUQWBS-SVHRXORXSA-N 0.000 description 11
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
• 239000007810 chemical reaction solvent Substances 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 239000000843 powder Substances 0.000 description 10
• 238000003786 synthesis reaction Methods 0.000 description 10
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 238000005886 esterification reaction Methods 0.000 description 9
• OQSPTEXJCKFBQS-KGLIPLIRSA-N (2,5-dioxopyrrolidin-1-yl) (2s,5r)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carboxylate Chemical compound O=C([C@H]1N2C[C@@](CC1)(N(C2=O)OCC=1C=CC=CC=1)[H])ON1C(=O)CCC1=O OQSPTEXJCKFBQS-KGLIPLIRSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
• SMCWNPAVVQIDBM-UHFFFAOYSA-N piperidine-1,2-dicarboxylic acid Chemical compound OC(=O)C1CCCCN1C(O)=O SMCWNPAVVQIDBM-UHFFFAOYSA-N 0.000 description 8
• BQPCLIKHAUTLSX-ZJUUUORDSA-N tert-butyl n-[2-[[(2s,5r)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]oxyethyl]carbamate Chemical compound C1N2[C@H](C(=O)NOCCNC(=O)OC(C)(C)C)CC[C@@]1([H])N(O)C2=O BQPCLIKHAUTLSX-ZJUUUORDSA-N 0.000 description 8
• MEQZWILNPLMCMK-SJORKVTESA-N tert-butyl n-[2-[[(2s,5r)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]oxyethyl]carbamate Chemical compound C([C@]1(CC[C@H]2C(=O)NOCCNC(=O)OC(C)(C)C)[H])N2C(=O)N1OCC1=CC=CC=C1 MEQZWILNPLMCMK-SJORKVTESA-N 0.000 description 8
• 0 *[C@](CC[C@]1C(O)=O)CN1P Chemical compound *[C@](CC[C@]1C(O)=O)CN1P 0.000 description 7
• 230000032050 esterification Effects 0.000 description 7
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• 241000209094 Oryza Species 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• 150000008065 acid anhydrides Chemical class 0.000 description 6
• DIZSYIFRCBQNST-RTWAWAEBSA-N benzyl N-[2-[[(2S,5R)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]oxyethyl]carbamate Chemical compound O=C(NCCONC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1)OCc1ccccc1 DIZSYIFRCBQNST-RTWAWAEBSA-N 0.000 description 6
• 238000010511 deprotection reaction Methods 0.000 description 6
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
• OZJJFJCEUKOVEH-QYZOEREBSA-N tert-butyl (2s)-2-[[[(2s,5r)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]oxymethyl]azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H]1CONC(=O)[C@H]1N(C(=O)N2OCC=3C=CC=CC=3)C[C@H]2CC1 OZJJFJCEUKOVEH-QYZOEREBSA-N 0.000 description 6
• MCIMNOZHBSHJFI-QYZOEREBSA-N tert-butyl (3s)-3-[[(2s,5r)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]oxypyrrolidine-1-carboxylate Chemical compound O=C([C@H]1N2C[C@@](CC1)(N(C2=O)OCC=1C=CC=CC=1)[H])NO[C@H]1CCN(C(=O)OC(C)(C)C)C1 MCIMNOZHBSHJFI-QYZOEREBSA-N 0.000 description 6
• MIGHPCZQXCOMLR-MOPGFXCFSA-N tert-butyl 3-[[[(2s,5r)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]oxymethyl]azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1CONC(=O)[C@H]1N(C(=O)N2OCC=3C=CC=CC=3)C[C@H]2CC1 MIGHPCZQXCOMLR-MOPGFXCFSA-N 0.000 description 6
• JARUJUAWDHGQMZ-MSOLQXFVSA-N tert-butyl n-methyl-n-[2-[[(2s,5r)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]oxyethyl]carbamate Chemical compound C([C@H]1CC[C@H]2C(=O)NOCCN(C)C(=O)OC(C)(C)C)N2C(=O)N1OCC1=CC=CC=C1 JARUJUAWDHGQMZ-MSOLQXFVSA-N 0.000 description 6
• ULSUSPWOEQWMOS-DBHNTLKXSA-N (2S,5R)-2-[(3aS,7aR)-1,3-dioxo-3a,4,7,7a-tetrahydroisoindol-2-yl]-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid Chemical compound OC(=O)[C@@]1(CC[C@@H]2CN1C(=O)N2OCc1ccccc1)N1C(=O)[C@H]2CC=CC[C@H]2C1=O ULSUSPWOEQWMOS-DBHNTLKXSA-N 0.000 description 5
• FBEYQRUEFGRFNJ-MOPGFXCFSA-N (2S,5R)-N-benzyl-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide Chemical compound C(C1=CC=CC=C1)NC(=O)[C@H]1N2C(N([C@H](CC1)C2)OCC1=CC=CC=C1)=O FBEYQRUEFGRFNJ-MOPGFXCFSA-N 0.000 description 5
• PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 5
• 235000007164 Oryza sativa Nutrition 0.000 description 5
• 150000007960 acetonitrile Chemical class 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 125000006517 heterocyclyl carbonyl group Chemical group 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 235000011181 potassium carbonates Nutrition 0.000 description 5
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• UDDLRRLHDNTWHG-JQHSSLGASA-N tert-butyl N-[(2S)-2-[[(2S,5R)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]oxypropyl]carbamate Chemical compound C[C@@H](CNC(=O)OC(C)(C)C)ONC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1 UDDLRRLHDNTWHG-JQHSSLGASA-N 0.000 description 1
• XZFPEJPLHUGGFS-UXHICEINSA-N tert-butyl N-[2-[[(2S,5R)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]oxyethyl]-N-propylcarbamate Chemical compound CCCN(CCONC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1)C(=O)OC(C)(C)C XZFPEJPLHUGGFS-UXHICEINSA-N 0.000 description 1
• ULIRSEWRKWGLAO-MOPGFXCFSA-N tert-butyl N-ethyl-N-[2-[[(2S,5R)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]oxyethyl]carbamate Chemical compound CCN(CCONC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1)C(=O)OC(C)(C)C ULIRSEWRKWGLAO-MOPGFXCFSA-N 0.000 description 1
• SQGVTSILTDRAAI-UHFFFAOYSA-N tert-butyl n-(2-aminooxyethyl)-n-methylcarbamate Chemical compound NOCCN(C)C(=O)OC(C)(C)C SQGVTSILTDRAAI-UHFFFAOYSA-N 0.000 description 1
• PIUNKYQLTUILMS-UHFFFAOYSA-N tert-butyl n-(2-aminooxyethyl)-n-propan-2-ylcarbamate Chemical compound NOCCN(C(C)C)C(=O)OC(C)(C)C PIUNKYQLTUILMS-UHFFFAOYSA-N 0.000 description 1
• QNYPOLKQWXCIGA-UHFFFAOYSA-N tert-butyl n-(3-aminooxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCON QNYPOLKQWXCIGA-UHFFFAOYSA-N 0.000 description 1
• SWALAYUOXONVQW-ZCFIWIBFSA-N tert-butyl n-[(2r)-1-aminooxypropan-2-yl]carbamate Chemical compound NOC[C@@H](C)NC(=O)OC(C)(C)C SWALAYUOXONVQW-ZCFIWIBFSA-N 0.000 description 1
• SWALAYUOXONVQW-LURJTMIESA-N tert-butyl n-[(2s)-1-aminooxypropan-2-yl]carbamate Chemical compound NOC[C@H](C)NC(=O)OC(C)(C)C SWALAYUOXONVQW-LURJTMIESA-N 0.000 description 1
• 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
• RPIXOLUIHUFDOY-UHFFFAOYSA-N thian-4-amine Chemical compound NC1CCSCC1 RPIXOLUIHUFDOY-UHFFFAOYSA-N 0.000 description 1
• AJZGFFKDLABHDD-UHFFFAOYSA-N thiazinane Chemical compound C1CCSNC1 AJZGFFKDLABHDD-UHFFFAOYSA-N 0.000 description 1
• CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
• JWCVYQRPINPYQJ-UHFFFAOYSA-N thiepane Chemical compound C1CCCSCC1 JWCVYQRPINPYQJ-UHFFFAOYSA-N 0.000 description 1
• GBNRIMMKLMTDLW-UHFFFAOYSA-N thiolan-3-amine Chemical compound NC1CCSC1 GBNRIMMKLMTDLW-UHFFFAOYSA-N 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• RKEYKDXXZCICFZ-UHFFFAOYSA-N trans-5-OH-L-pipecolic acid Natural products OC1CCC(C(O)=O)NC1 RKEYKDXXZCICFZ-UHFFFAOYSA-N 0.000 description 1
• 125000004665 trialkylsilyl group Chemical group 0.000 description 1
• LWZYUGKULMDWHY-UHFFFAOYSA-N trichloromethoxycarbamic acid Chemical compound OC(=O)NOC(Cl)(Cl)Cl LWZYUGKULMDWHY-UHFFFAOYSA-N 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1