SG190007A1 - Monobactams - Google Patents

Info

Publication number

SG190007A1

SG190007A1 SG2013031752A SG2013031752A SG190007A1 SG 190007 A1 SG190007 A1 SG 190007A1 SG 2013031752 A SG2013031752 A SG 2013031752A SG 2013031752 A SG2013031752 A SG 2013031752A SG 190007 A1 SG190007 A1 SG 190007A1

Authority

SG

Singapore

Prior art keywords

mmol

formula

treated

yield

preparation

Prior art date

2010-11-29

Links

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• 229940041009 monobactams Drugs 0.000 title description 7
• 208000035143 Bacterial infection Diseases 0.000 claims abstract description 13
• 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 13
• 150000001875 compounds Chemical class 0.000 claims description 227
• 229910052739 hydrogen Inorganic materials 0.000 claims description 96
• 239000001257 hydrogen Substances 0.000 claims description 96
• 238000000034 method Methods 0.000 claims description 91
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 89
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 88
• 125000000217 alkyl group Chemical group 0.000 claims description 54
• 229910052799 carbon Inorganic materials 0.000 claims description 44
• -1 (1-(2-aminothiazol-4-yl)-2-(((2S,3R)-2-((3- ((1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl)ureido)methyl)-4-oxo-1- sulfoazetidin-3-yl)amino)-2-oxoethylidene )amino Chemical group 0.000 claims description 43
• 150000003839 salts Chemical class 0.000 claims description 39
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
• 239000003814 drug Substances 0.000 claims description 25
• 125000000623 heterocyclic group Chemical group 0.000 claims description 14
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 13
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 13
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 12
• 238000004519 manufacturing process Methods 0.000 claims description 12
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 9
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 9
• 125000004432 carbon atom Chemical group C* 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 150000003852 triazoles Chemical class 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 5
• WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical class O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 457
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 361
• 239000000243 solution Substances 0.000 description 246
• 239000007787 solid Substances 0.000 description 239
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 212
• 239000000203 mixture Substances 0.000 description 211
• 238000002360 preparation method Methods 0.000 description 208
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 183
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 180
• 238000005481 NMR spectroscopy Methods 0.000 description 160
• 235000019439 ethyl acetate Nutrition 0.000 description 153
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 142
• 239000011541 reaction mixture Substances 0.000 description 137
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 132
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 131
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 98
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 93
• 238000006243 chemical reaction Methods 0.000 description 93
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
• 239000002904 solvent Substances 0.000 description 83
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 74
• 239000012044 organic layer Substances 0.000 description 74
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 72
• 239000010410 layer Substances 0.000 description 70
• 238000004587 chromatography analysis Methods 0.000 description 69
• 239000000741 silica gel Substances 0.000 description 66
• 229910002027 silica gel Inorganic materials 0.000 description 66
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 64
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 62
• 208000015181 infectious disease Diseases 0.000 description 61
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 60
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
• 239000000725 suspension Substances 0.000 description 56
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 55
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 51
• 239000013058 crude material Substances 0.000 description 51
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 48
• 229910052757 nitrogen Inorganic materials 0.000 description 48
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 41
• 229910052938 sodium sulfate Inorganic materials 0.000 description 41
• 235000011152 sodium sulphate Nutrition 0.000 description 41
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 41
• 239000000706 filtrate Substances 0.000 description 40
• 238000001914 filtration Methods 0.000 description 40
• 239000012267 brine Substances 0.000 description 37
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 36
• 150000001721 carbon Chemical group 0.000 description 36
• 235000019253 formic acid Nutrition 0.000 description 36
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 36
• 239000012043 crude product Substances 0.000 description 34
• 235000019441 ethanol Nutrition 0.000 description 34
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 33
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 32
• 235000019341 magnesium sulphate Nutrition 0.000 description 32
• 238000003756 stirring Methods 0.000 description 31
• 239000012065 filter cake Substances 0.000 description 30
• 235000017557 sodium bicarbonate Nutrition 0.000 description 29
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 29
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 26
• 239000000047 product Substances 0.000 description 26
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 25
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 25
• 239000002002 slurry Substances 0.000 description 25
• 239000003607 modifier Substances 0.000 description 24
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 24
• RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 23
• 229960004592 isopropanol Drugs 0.000 description 22
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 21
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
• 229940086542 triethylamine Drugs 0.000 description 20
• 230000015572 biosynthetic process Effects 0.000 description 19
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 17
• 238000004128 high performance liquid chromatography Methods 0.000 description 17
• 230000002496 gastric effect Effects 0.000 description 15
• 229920006395 saturated elastomer Polymers 0.000 description 15
• 208000027096 gram-negative bacterial infections Diseases 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
• 238000010511 deprotection reaction Methods 0.000 description 13
• 239000012071 phase Substances 0.000 description 13
• 229910000027 potassium carbonate Inorganic materials 0.000 description 13
• 230000002829 reductive effect Effects 0.000 description 13
• 238000003786 synthesis reaction Methods 0.000 description 13
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 12
• 229940079593 drug Drugs 0.000 description 12
• 239000006260 foam Substances 0.000 description 12
• 125000006239 protecting group Chemical group 0.000 description 12
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
• 230000006103 sulfonylation Effects 0.000 description 12
• 238000005694 sulfonylation reaction Methods 0.000 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 239000000010 aprotic solvent Substances 0.000 description 11
• 239000012467 final product Substances 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 235000019198 oils Nutrition 0.000 description 11
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
• 150000001412 amines Chemical class 0.000 description 10
• 239000000543 intermediate Substances 0.000 description 10
• 230000014759 maintenance of location Effects 0.000 description 10
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
• 241000588626 Acinetobacter baumannii Species 0.000 description 9
• 241000588724 Escherichia coli Species 0.000 description 9
• 241000588747 Klebsiella pneumoniae Species 0.000 description 9
• 208000032376 Lung infection Diseases 0.000 description 9
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
• 241000589517 Pseudomonas aeruginosa Species 0.000 description 9
• 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 238000001514 detection method Methods 0.000 description 9
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 9
• 125000001424 substituent group Chemical group 0.000 description 9
• 230000009885 systemic effect Effects 0.000 description 9
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• 208000031729 Bacteremia Diseases 0.000 description 8
• 241000894006 Bacteria Species 0.000 description 8
• 208000014912 Central Nervous System Infections Diseases 0.000 description 8
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• 201000003883 Cystic fibrosis Diseases 0.000 description 8
• 206010060803 Diabetic foot infection Diseases 0.000 description 8
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
• 208000008745 Healthcare-Associated Pneumonia Diseases 0.000 description 8
• 241000590002 Helicobacter pylori Species 0.000 description 8
• 208000036209 Intraabdominal Infections Diseases 0.000 description 8
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
• 206010031252 Osteomyelitis Diseases 0.000 description 8
• 208000008469 Peptic Ulcer Diseases 0.000 description 8
• 206010035664 Pneumonia Diseases 0.000 description 8
• 206010040047 Sepsis Diseases 0.000 description 8
• 206010062255 Soft tissue infection Diseases 0.000 description 8
• 206010052428 Wound Diseases 0.000 description 8
• 239000003781 beta lactamase inhibitor Substances 0.000 description 8
• 229940126813 beta-lactamase inhibitor Drugs 0.000 description 8
• 208000025222 central nervous system infectious disease Diseases 0.000 description 8
• 238000005859 coupling reaction Methods 0.000 description 8
• 206010014665 endocarditis Diseases 0.000 description 8
• 239000000284 extract Substances 0.000 description 8
• 229910052736 halogen Inorganic materials 0.000 description 8
• 150000002367 halogens Chemical class 0.000 description 8
• 229940037467 helicobacter pylori Drugs 0.000 description 8
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
• 208000011906 peptic ulcer disease Diseases 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 206010040872 skin infection Diseases 0.000 description 8
• 125000001425 triazolyl group Chemical group 0.000 description 8
• 208000019206 urinary tract infection Diseases 0.000 description 8
• JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
• 208000005623 Carcinogenesis Diseases 0.000 description 7
• 208000001860 Eye Infections Diseases 0.000 description 7
• 208000027418 Wounds and injury Diseases 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 239000003242 anti bacterial agent Substances 0.000 description 7
• 230000036952 cancer formation Effects 0.000 description 7
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 7
• 231100000504 carcinogenesis Toxicity 0.000 description 7
• 239000000460 chlorine Substances 0.000 description 7
• 125000004093 cyano group Chemical group *C#N 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• 150000003952 β-lactams Chemical class 0.000 description 7
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
• 239000005909 Kieselgur Substances 0.000 description 6
• 229910019142 PO4 Inorganic materials 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-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
• 125000003545 alkoxy group Chemical group 0.000 description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 description 6
• 125000004430 oxygen atom Chemical group O* 0.000 description 6
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
• 239000010452 phosphate Substances 0.000 description 6
• 239000000651 prodrug Substances 0.000 description 6
• 229940002612 prodrug Drugs 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• 238000000926 separation method Methods 0.000 description 6
• 239000011780 sodium chloride Substances 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• 229910052717 sulfur Chemical group 0.000 description 6
• 125000004434 sulfur atom Chemical group 0.000 description 6
• FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 6
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
• 238000003828 vacuum filtration Methods 0.000 description 6
• 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 6
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
• 229930186147 Cephalosporin Natural products 0.000 description 5
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 5
• 230000000844 anti-bacterial effect Effects 0.000 description 5
• MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical group O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 5
• 229940124587 cephalosporin Drugs 0.000 description 5
• 150000001780 cephalosporins Chemical class 0.000 description 5
• 230000008878 coupling Effects 0.000 description 5
• 238000010168 coupling process Methods 0.000 description 5
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• AFDQGRURHDVABZ-UHFFFAOYSA-N n,n-dimethylformamide;sulfur trioxide Chemical compound O=S(=O)=O.CN(C)C=O AFDQGRURHDVABZ-UHFFFAOYSA-N 0.000 description 5
• 239000011698 potassium fluoride Substances 0.000 description 5
• 239000000376 reactant Substances 0.000 description 5
• 238000010898 silica gel chromatography Methods 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 4
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
• 239000005695 Ammonium acetate Substances 0.000 description 4
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• 102100024452 DNA-directed RNA polymerase III subunit RPC1 Human genes 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• 101000689002 Homo sapiens DNA-directed RNA polymerase III subunit RPC1 Proteins 0.000 description 4
• URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
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