NZ577214A - Fused substituted aminopyrrolidine derivatives useful as antibacterial reagents - Google Patents

Info

Publication number

NZ577214A

NZ577214A NZ577214A NZ57721407A NZ577214A NZ 577214 A NZ577214 A NZ 577214A NZ 577214 A NZ577214 A NZ 577214A NZ 57721407 A NZ57721407 A NZ 57721407A NZ 577214 A NZ577214 A NZ 577214A

Authority

NZ

New Zealand

Prior art keywords

group

formula

compound

carbon atoms

amino

Prior art date

2007-01-05

Links

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• 230000000844 anti-bacterial effect Effects 0.000 title abstract description 22
• SBMSLRMNBSMKQC-UHFFFAOYSA-N pyrrolidin-1-amine Chemical class NN1CCCC1 SBMSLRMNBSMKQC-UHFFFAOYSA-N 0.000 title description 20
• 239000003153 chemical reaction reagent Substances 0.000 title description 13
• 150000001875 compounds Chemical class 0.000 claims abstract description 274
• 239000003814 drug Substances 0.000 claims abstract description 34
• 125000004432 carbon atom Chemical group C* 0.000 claims description 201
• -1 6-amino-3,5-difluoropyridin-2-yl group Chemical group 0.000 claims description 157
• 125000003277 amino group Chemical group 0.000 claims description 88
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 85
• 125000004122 cyclic group Chemical group 0.000 claims description 82
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 77
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 53
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 50
• 229910052731 fluorine Chemical group 0.000 claims description 50
• 125000001153 fluoro group Chemical group F* 0.000 claims description 48
• 230000036961 partial effect Effects 0.000 claims description 46
• 150000003839 salts Chemical class 0.000 claims description 40
• 229910052739 hydrogen Inorganic materials 0.000 claims description 31
• 239000001257 hydrogen Substances 0.000 claims description 28
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 27
• 239000003242 anti bacterial agent Substances 0.000 claims description 26
• 229910052801 chlorine Inorganic materials 0.000 claims description 22
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 21
• 125000002619 bicyclic group Chemical group 0.000 claims description 20
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 20
• 125000004429 atom Chemical group 0.000 claims description 19
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 16
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 16
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 16
• 208000015181 infectious disease Diseases 0.000 claims description 15
• 239000000470 constituent Substances 0.000 claims description 13
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 7
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 5
• 229940124597 therapeutic agent Drugs 0.000 claims description 5
• 239000004480 active ingredient Substances 0.000 claims description 4
• 125000006419 fluorocyclopropyl group Chemical group 0.000 claims description 4
• 238000000034 method Methods 0.000 abstract description 22
• 229940079593 drug Drugs 0.000 abstract description 18
• 238000002360 preparation method Methods 0.000 abstract description 12
• 239000003755 preservative agent Substances 0.000 abstract description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 414
• 239000000243 solution Substances 0.000 description 293
• 125000001424 substituent group Chemical group 0.000 description 212
• 239000000203 mixture Substances 0.000 description 201
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 201
• 238000006243 chemical reaction Methods 0.000 description 163
• 230000002829 reductive effect Effects 0.000 description 155
• 125000000217 alkyl group Chemical group 0.000 description 154
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 148
• 229940093499 ethyl acetate Drugs 0.000 description 140
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 138
• 235000019439 ethyl acetate Nutrition 0.000 description 137
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 115
• 239000002904 solvent Substances 0.000 description 114
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 107
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 102
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 93
• 125000005843 halogen group Chemical group 0.000 description 89
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 81
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 79
• 239000012044 organic layer Substances 0.000 description 72
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
• 125000003545 alkoxy group Chemical group 0.000 description 69
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 68
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 65
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 64
• 238000001914 filtration Methods 0.000 description 60
• 101150041968 CDC13 gene Proteins 0.000 description 59
• 239000012267 brine Substances 0.000 description 57
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 57
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 56
• 238000010898 silica gel chromatography Methods 0.000 description 56
• 239000007787 solid Substances 0.000 description 55
• 239000000706 filtrate Substances 0.000 description 53
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 53
• 239000002253 acid Substances 0.000 description 52
• 238000000605 extraction Methods 0.000 description 52
• 125000006239 protecting group Chemical group 0.000 description 52
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 48
• 238000005160 1H NMR spectroscopy Methods 0.000 description 47
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
• 238000001816 cooling Methods 0.000 description 38
• 238000005481 NMR spectroscopy Methods 0.000 description 36
• 239000003054 catalyst Substances 0.000 description 36
• 239000012230 colorless oil Substances 0.000 description 36
• 125000000753 cycloalkyl group Chemical group 0.000 description 36
• LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 34
• 239000003921 oil Substances 0.000 description 31
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
• 125000003342 alkenyl group Chemical group 0.000 description 28
• 229910052799 carbon Inorganic materials 0.000 description 28
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 27
• 230000003287 optical effect Effects 0.000 description 27
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 27
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
• 239000010410 layer Substances 0.000 description 26
• 238000003756 stirring Methods 0.000 description 26
• 239000012299 nitrogen atmosphere Substances 0.000 description 24
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 23
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 22
• 239000000543 intermediate Substances 0.000 description 22
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
• 125000004414 alkyl thio group Chemical group 0.000 description 21
• 125000001072 heteroaryl group Chemical group 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 20
• 238000010992 reflux Methods 0.000 description 20
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
• 235000019341 magnesium sulphate Nutrition 0.000 description 19
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 19
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
• 150000001721 carbon Chemical group 0.000 description 18
• 125000004494 ethyl ester group Chemical group 0.000 description 18
• 229910052757 nitrogen Inorganic materials 0.000 description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 18
• 239000002585 base Substances 0.000 description 17
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 17
• 238000007363 ring formation reaction Methods 0.000 description 17
• 229910052717 sulfur Inorganic materials 0.000 description 17
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 16
• 150000001412 amines Chemical class 0.000 description 16
• 150000004702 methyl esters Chemical class 0.000 description 16
• 238000000926 separation method Methods 0.000 description 16
• 125000004434 sulfur atom Chemical group 0.000 description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 15
• 125000002252 acyl group Chemical group 0.000 description 15
• 239000012298 atmosphere Substances 0.000 description 15
• 238000010511 deprotection reaction Methods 0.000 description 15
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 15
• 230000000694 effects Effects 0.000 description 15
• 150000002148 esters Chemical class 0.000 description 15
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
• UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 description 15
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 15
• 150000007660 quinolones Chemical class 0.000 description 15
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 14
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
• 239000013522 chelant Substances 0.000 description 14
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 14
• XWAHLXHVEMYNMY-UHFFFAOYSA-N tert-butyl pyrrolidine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1CCNC1 XWAHLXHVEMYNMY-UHFFFAOYSA-N 0.000 description 14
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
• 230000003197 catalytic effect Effects 0.000 description 13
• 125000004185 ester group Chemical group 0.000 description 13
• 238000010438 heat treatment Methods 0.000 description 13
• 230000009467 reduction Effects 0.000 description 13
• 238000006722 reduction reaction Methods 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• 125000000304 alkynyl group Chemical group 0.000 description 12
• 150000001408 amides Chemical class 0.000 description 12
• 201000010099 disease Diseases 0.000 description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 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
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
• 125000003118 aryl group Chemical group 0.000 description 11
• 230000015572 biosynthetic process Effects 0.000 description 11
• 239000013078 crystal Substances 0.000 description 11
• 239000012046 mixed solvent Substances 0.000 description 11
• 238000003786 synthesis reaction Methods 0.000 description 11
• XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid Chemical class C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 description 10
• FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 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 10
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 10
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• 229910052708 sodium Inorganic materials 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
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
• 238000006460 hydrolysis reaction Methods 0.000 description 9
• 239000000843 powder Substances 0.000 description 9
• 230000002194 synthesizing effect Effects 0.000 description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 9
• UZHVXJZEHGSWQV-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrole Chemical group C1NCC2CCCC21 UZHVXJZEHGSWQV-UHFFFAOYSA-N 0.000 description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• 206010034972 Photosensitivity reaction Diseases 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
• 238000006482 condensation reaction Methods 0.000 description 8
• 238000001035 drying Methods 0.000 description 8
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 8
• 230000007062 hydrolysis Effects 0.000 description 8
• 150000003951 lactams Chemical class 0.000 description 8
• 239000003446 ligand Substances 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
• XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 8
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 8
• 241000894006 Bacteria Species 0.000 description 7
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 7
• 108010016626 Dipeptides Proteins 0.000 description 7
• 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 7
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 7
• FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical class CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 description 7
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
• 230000002378 acidificating effect Effects 0.000 description 7
• 235000001014 amino acid Nutrition 0.000 description 7
• 229940024606 amino acid Drugs 0.000 description 7
• 150000001413 amino acids Chemical class 0.000 description 7
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 7
• 229910052736 halogen Inorganic materials 0.000 description 7
• 150000002431 hydrogen Chemical class 0.000 description 7
• 239000012279 sodium borohydride Substances 0.000 description 7
• 229910000033 sodium borohydride Inorganic materials 0.000 description 7
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 7
• 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 6
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 230000005856 abnormality Effects 0.000 description 6
• UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 6
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 6
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 6
• 239000012948 isocyanate Substances 0.000 description 6
• 150000002513 isocyanates Chemical class 0.000 description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical class CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000000047 product Substances 0.000 description 6
• 238000001953 recrystallisation Methods 0.000 description 6
• 230000035945 sensitivity Effects 0.000 description 6
• 239000000741 silica gel Substances 0.000 description 6
• 229910002027 silica gel Inorganic materials 0.000 description 6
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 6
• PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 5
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 5
• FTDYEJBHNFGOLF-UHFFFAOYSA-N 2-methoxy-4-oxo-3h-quinoline-3-carboxylic acid Chemical compound C1=CC=C2C(=O)C(C(O)=O)C(OC)=NC2=C1 FTDYEJBHNFGOLF-UHFFFAOYSA-N 0.000 description 5
• 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 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
• 238000006969 Curtius rearrangement reaction Methods 0.000 description 5
• 241000588724 Escherichia coli Species 0.000 description 5
• HEMHJVSKTPXQMS-DYCDLGHISA-M Sodium hydroxide-d Chemical compound [Na+].[2H][O-] HEMHJVSKTPXQMS-DYCDLGHISA-M 0.000 description 5
• 239000013543 active substance Substances 0.000 description 5
• 239000000654 additive Substances 0.000 description 5
• 230000000996 additive effect Effects 0.000 description 5
• 229910052783 alkali metal Inorganic materials 0.000 description 5
• 125000004849 alkoxymethyl group Chemical group 0.000 description 5
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 5
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
• CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 238000004587 chromatography analysis Methods 0.000 description 5
• 230000005494 condensation Effects 0.000 description 5
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
• 125000006575 electron-withdrawing group Chemical group 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
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