IL95331A - Azabicyclo quinolone carboxylic acids and their use in the preparation of drugs for the treatment of fungal diseases - Google Patents

Info

Publication number

IL95331A

IL95331A IL9533190A IL9533190A IL95331A IL 95331 A IL95331 A IL 95331A IL 9533190 A IL9533190 A IL 9533190A IL 9533190 A IL9533190 A IL 9533190A IL 95331 A IL95331 A IL 95331A

Authority

IL

Israel

Prior art keywords

mmol

azabicyclo

methyl

carboxylic acid

hexane

Prior art date

1989-08-16

Links

• Espacenet
• Global Dossier
• Discuss

• 238000002360 preparation method Methods 0.000 title claims description 36
• 208000035143 Bacterial infection Diseases 0.000 title claims description 6
• 208000022362 bacterial infectious disease Diseases 0.000 title claims description 5
• 239000003814 drug Substances 0.000 title claims description 5
• -1 quinolone carboxylic acids Chemical class 0.000 title abstract description 184
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 78
• 239000001257 hydrogen Substances 0.000 claims abstract description 49
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 49
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 24
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 21
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 17
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 14
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 12
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 11
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 8
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
• 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 7
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
• 150000001768 cations Chemical class 0.000 claims abstract description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 4
• AQIAIZBHFAKICS-UHFFFAOYSA-N methylaminomethyl Chemical compound [CH2]NC AQIAIZBHFAKICS-UHFFFAOYSA-N 0.000 claims abstract description 4
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
• 239000001301 oxygen Substances 0.000 claims abstract description 4
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 3
• 229920002554 vinyl polymer Polymers 0.000 claims abstract description 3
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims abstract 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims abstract 2
• 125000006519 CCH3 Chemical group 0.000 claims abstract 2
• 125000003545 alkoxy group Chemical group 0.000 claims abstract 2
• 150000001875 compounds Chemical class 0.000 claims description 256
• 239000002253 acid Substances 0.000 claims description 24
• 150000002431 hydrogen Chemical class 0.000 claims description 24
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 20
• 125000001424 substituent group Chemical group 0.000 claims description 18
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
• 150000003839 salts Chemical class 0.000 claims description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
• 125000003277 amino group Chemical group 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 239000000651 prodrug Substances 0.000 claims description 4
• 229940002612 prodrug Drugs 0.000 claims description 4
• 125000001246 bromo group Chemical group Br* 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
• 125000001153 fluoro group Chemical group F* 0.000 claims description 2
• XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 abstract description 5
• 229910052794 bromium Inorganic materials 0.000 abstract description 2
• 229910052801 chlorine Inorganic materials 0.000 abstract description 2
• 229910052731 fluorine Inorganic materials 0.000 abstract description 2
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 1
• 239000000047 product Substances 0.000 description 147
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 138
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
• 239000000243 solution Substances 0.000 description 130
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
• 238000005481 NMR spectroscopy Methods 0.000 description 109
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 109
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 100
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
• 101150041968 CDC13 gene Proteins 0.000 description 91
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 91
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
• 238000000034 method Methods 0.000 description 84
• 239000007787 solid Substances 0.000 description 80
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 70
• 239000000203 mixture Substances 0.000 description 67
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
• 125000004494 ethyl ester group Chemical group 0.000 description 61
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
• 239000003921 oil Substances 0.000 description 55
• 239000002904 solvent Substances 0.000 description 52
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 49
• 239000011541 reaction mixture Substances 0.000 description 49
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
• 229940086542 triethylamine Drugs 0.000 description 46
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 45
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 44
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 43
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
• 238000006243 chemical reaction Methods 0.000 description 42
• 239000012044 organic layer Substances 0.000 description 41
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 40
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 38
• 238000005160 1H NMR spectroscopy Methods 0.000 description 34
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 34
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 34
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 32
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
• 229910052938 sodium sulfate Inorganic materials 0.000 description 29
• 235000011152 sodium sulphate Nutrition 0.000 description 29
• 238000004440 column chromatography Methods 0.000 description 28
• 238000010992 reflux Methods 0.000 description 28
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 239000000706 filtrate Substances 0.000 description 27
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 27
• 239000012280 lithium aluminium hydride Substances 0.000 description 25
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 24
• 230000009467 reduction Effects 0.000 description 24
• 238000006722 reduction reaction Methods 0.000 description 24
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
• 238000000354 decomposition reaction Methods 0.000 description 22
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 22
• 238000005888 cyclopropanation reaction Methods 0.000 description 21
• YVPJCJLMRRTDMQ-UHFFFAOYSA-N ethyl diazoacetate Chemical compound CCOC(=O)C=[N+]=[N-] YVPJCJLMRRTDMQ-UHFFFAOYSA-N 0.000 description 21
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
• 235000019341 magnesium sulphate Nutrition 0.000 description 21
• 150000003138 primary alcohols Chemical class 0.000 description 21
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 20
• 239000000908 ammonium hydroxide Substances 0.000 description 20
• 238000001914 filtration Methods 0.000 description 20
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 19
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
• 229920006395 saturated elastomer Polymers 0.000 description 18
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 16
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• 239000002585 base Substances 0.000 description 15
• 239000012267 brine Substances 0.000 description 15
• 230000002829 reductive effect Effects 0.000 description 15
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 14
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 14
• 229910052763 palladium Inorganic materials 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
• 239000010410 layer Substances 0.000 description 13
• 239000000463 material Substances 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
• 229940098779 methanesulfonic acid Drugs 0.000 description 12
• 238000000746 purification Methods 0.000 description 12
• SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 12
• 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 12
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 11
• 238000001953 recrystallisation Methods 0.000 description 11
• 239000000741 silica gel Substances 0.000 description 11
• 229910002027 silica gel Inorganic materials 0.000 description 11
• 239000007858 starting material Substances 0.000 description 11
• 150000001412 amines Chemical class 0.000 description 10
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 10
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 10
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 10
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 10
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 9
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 9
• 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 9
• HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 8
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 230000002378 acidificating effect Effects 0.000 description 8
• 239000012230 colorless oil Substances 0.000 description 8
• 238000006352 cycloaddition reaction Methods 0.000 description 8
• 238000005984 hydrogenation reaction Methods 0.000 description 8
• 150000002576 ketones Chemical class 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• 150000003335 secondary amines Chemical class 0.000 description 8
• HGWUUOXXAIISDB-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane Chemical compound C1NCC2CC21 HGWUUOXXAIISDB-UHFFFAOYSA-N 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
• 230000005595 deprotonation Effects 0.000 description 7
• 238000010537 deprotonation reaction Methods 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• 230000007062 hydrolysis Effects 0.000 description 7
• 238000006460 hydrolysis reaction Methods 0.000 description 7
• 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 7
• 150000002825 nitriles Chemical class 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 238000012546 transfer Methods 0.000 description 7
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical group CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
• 239000005909 Kieselgur Substances 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
• 125000002252 acyl group Chemical group 0.000 description 6
• 238000010640 amide synthesis reaction Methods 0.000 description 6
• 239000000538 analytical sample Substances 0.000 description 6
• 238000006555 catalytic reaction Methods 0.000 description 6
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 6
• WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 6
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 6
• 238000012545 processing Methods 0.000 description 6
• 238000010791 quenching Methods 0.000 description 6
• 238000010898 silica gel chromatography Methods 0.000 description 6
• NMJRXNUMGKZPHG-UHFFFAOYSA-N (3-benzyl-3-azabicyclo[3.1.0]hexan-6-yl)methanol Chemical compound C1C2C(CO)C2CN1CC1=CC=CC=C1 NMJRXNUMGKZPHG-UHFFFAOYSA-N 0.000 description 5
• BOHSMHNKEIRAEH-UHFFFAOYSA-N 3-benzyl-3-azabicyclo[3.1.0]hexane-1-carbonitrile Chemical compound C1C2(C#N)CC2CN1CC1=CC=CC=C1 BOHSMHNKEIRAEH-UHFFFAOYSA-N 0.000 description 5
• 150000005228 3‐azabicyclo[3.1.0]hexanes Chemical class 0.000 description 5
• MZFQJBMXUXJUHF-UHFFFAOYSA-N 4-azabicyclo[4.1.0]heptane Chemical compound C1CNCC2CC21 MZFQJBMXUXJUHF-UHFFFAOYSA-N 0.000 description 5
• 238000006969 Curtius rearrangement reaction Methods 0.000 description 5
• 239000012448 Lithium borohydride Substances 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
• 150000001408 amides Chemical class 0.000 description 5
• 238000010533 azeotropic distillation Methods 0.000 description 5
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 5
• 239000003610 charcoal Substances 0.000 description 5
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 5
• 238000007327 hydrogenolysis reaction Methods 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 150000003141 primary amines Chemical class 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 239000012312 sodium hydride Substances 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• HGINADPHJQTSKN-UHFFFAOYSA-M 3-ethoxy-3-oxopropanoate Chemical compound CCOC(=O)CC([O-])=O HGINADPHJQTSKN-UHFFFAOYSA-M 0.000 description 4
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
• CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 4
• 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 4
• ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• 125000000539 amino acid group Chemical group 0.000 description 4
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 4
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
• 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 4
• 230000001404 mediated effect Effects 0.000 description 4
• DGEYTDCFMQMLTH-UHFFFAOYSA-N methanol;propan-2-ol Chemical compound OC.CC(C)O DGEYTDCFMQMLTH-UHFFFAOYSA-N 0.000 description 4
• ZMDGICHYDVYQDX-UHFFFAOYSA-N methylidenecarbamic acid Chemical compound OC(=O)N=C ZMDGICHYDVYQDX-UHFFFAOYSA-N 0.000 description 4
• 229910052750 molybdenum Inorganic materials 0.000 description 4
• 239000011733 molybdenum Substances 0.000 description 4
• 150000005054 naphthyridines Chemical class 0.000 description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
• 230000003647 oxidation Effects 0.000 description 4
• 238000007254 oxidation reaction Methods 0.000 description 4
• 229910000027 potassium carbonate Inorganic materials 0.000 description 4
• 230000000171 quenching effect Effects 0.000 description 4
• LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• 238000001665 trituration Methods 0.000 description 4
• UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 4
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
• 229910052772 Samarium Inorganic materials 0.000 description 3
• 238000006859 Swern oxidation reaction Methods 0.000 description 3
• AUALQMFGWLZREY-UHFFFAOYSA-N acetonitrile;methanol Chemical compound OC.CC#N AUALQMFGWLZREY-UHFFFAOYSA-N 0.000 description 3
• 235000019270 ammonium chloride Nutrition 0.000 description 3
• 239000003242 anti bacterial agent Substances 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• YWKYQRWNOXUYJK-UHFFFAOYSA-N benzyl 3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1CC=CCN1C(=O)OCC1=CC=CC=C1 YWKYQRWNOXUYJK-UHFFFAOYSA-N 0.000 description 3
• 125000002619 bicyclic group Chemical group 0.000 description 3
• 125000002091 cationic group Chemical group 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 239000007810 chemical reaction solvent Substances 0.000 description 3
• PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 239000013058 crude material Substances 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 238000006264 debenzylation reaction Methods 0.000 description 3
• 150000004985 diamines Chemical class 0.000 description 3
• 125000004185 ester group Chemical group 0.000 description 3
• 239000006260 foam Substances 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• 125000000623 heterocyclic group Chemical group 0.000 description 3
• 239000000543 intermediate Substances 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 3
• 238000006772 olefination reaction Methods 0.000 description 3
• 150000002923 oximes Chemical class 0.000 description 3
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• 238000006798 ring closing metathesis reaction Methods 0.000 description 3
• 238000007363 ring formation reaction Methods 0.000 description 3
• KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 description 3
• WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 150000003527 tetrahydropyrans Chemical group 0.000 description 3
• 238000007070 tosylation reaction Methods 0.000 description 3
• XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 2
• BYIORNOSWMDYSC-UHFFFAOYSA-N (3-benzyl-3-azabicyclo[3.1.0]hexan-2-yl)methanamine Chemical compound NCC1C2CC2CN1CC1=CC=CC=C1 BYIORNOSWMDYSC-UHFFFAOYSA-N 0.000 description 2
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 2
• MKRBAPNEJMFMHU-UHFFFAOYSA-N 1-benzylpyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1CC1=CC=CC=C1 MKRBAPNEJMFMHU-UHFFFAOYSA-N 0.000 description 2
• 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 2
• LAWHHRXCBUNWFI-UHFFFAOYSA-N 2-pentylpropanedioic acid Chemical compound CCCCCC(C(O)=O)C(O)=O LAWHHRXCBUNWFI-UHFFFAOYSA-N 0.000 description 2
• MDTVXRYDNXZXNZ-UHFFFAOYSA-N 3-(benzylamino)butanenitrile Chemical class N#CCC(C)NCC1=CC=CC=C1 MDTVXRYDNXZXNZ-UHFFFAOYSA-N 0.000 description 2
• COCNBXQWBCBUHL-UHFFFAOYSA-N 3-benzyl-3-azabicyclo[3.1.0]hexane-1-carboxylic acid Chemical compound C1C2(C(=O)O)CC2CN1CC1=CC=CC=C1 COCNBXQWBCBUHL-UHFFFAOYSA-N 0.000 description 2
• SFKGDXXYRFSCLI-UHFFFAOYSA-N 3-benzyl-3-azabicyclo[3.1.0]hexane-2-carbonitrile Chemical compound N#CC1C2CC2CN1CC1=CC=CC=C1 SFKGDXXYRFSCLI-UHFFFAOYSA-N 0.000 description 2
• ZMQAZKRRNYMOLW-UHFFFAOYSA-N 3-benzyl-3-azabicyclo[4.1.0]heptan-5-amine Chemical compound C1C2CC2C(N)CN1CC1=CC=CC=C1 ZMQAZKRRNYMOLW-UHFFFAOYSA-N 0.000 description 2
• BXRLWGXPSRYJDZ-UHFFFAOYSA-N 3-cyanoalanine Chemical compound OC(=O)C(N)CC#N BXRLWGXPSRYJDZ-UHFFFAOYSA-N 0.000 description 2
• WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 description 2
• ICSLZBSYUJAPNS-UHFFFAOYSA-N 3-phenylmethoxycarbonyl-3-azabicyclo[3.1.0]hexane-6-carboxylic acid Chemical compound C1C2C(C(=O)O)C2CN1C(=O)OCC1=CC=CC=C1 ICSLZBSYUJAPNS-UHFFFAOYSA-N 0.000 description 2
• CQPUZLMNORVQPG-UHFFFAOYSA-N 5-amino-1-cyclopropyl-6,7,8-trifluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)C=2C(N)=C(F)C(F)=C(F)C=2N1C1CC1 CQPUZLMNORVQPG-UHFFFAOYSA-N 0.000 description 2
• ZZCKTINYQRJIIU-UHFFFAOYSA-N 5-oxo-3-phenylmethoxycarbonyl-3-azabicyclo[4.1.0]heptane-7-carboxylic acid Chemical compound C1C(=O)C2C(C(=O)O)C2CN1C(=O)OCC1=CC=CC=C1 ZZCKTINYQRJIIU-UHFFFAOYSA-N 0.000 description 2
• WTCJJEJMYYASNT-UHFFFAOYSA-N 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C12=NC(Cl)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1=CC=C(F)C=C1F WTCJJEJMYYASNT-UHFFFAOYSA-N 0.000 description 2
• NVKWWNNJFKZNJO-UHFFFAOYSA-N 82419-35-0 Chemical compound O1CC(C)N2C=C(C(O)=O)C(=O)C3=C2C1=C(F)C(F)=C3 NVKWWNNJFKZNJO-UHFFFAOYSA-N 0.000 description 2
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
• VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
• BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
• 125000003047 N-acetyl group Chemical group 0.000 description 2
• 238000003527 Peterson olefination reaction Methods 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• HEMHJVSKTPXQMS-DYCDLGHISA-M Sodium hydroxide-d Chemical compound [Na+].[2H][O-] HEMHJVSKTPXQMS-DYCDLGHISA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
• 239000012346 acetyl chloride Substances 0.000 description 2
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 229910052783 alkali metal Inorganic materials 0.000 description 2
• 150000001340 alkali metals Chemical class 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 230000001580 bacterial effect Effects 0.000 description 2
• XSKKIFJNZPNVGO-UHFFFAOYSA-N benzyl 2,5-dihydropyrrole-1-carboxylate Chemical compound C1C=CCN1C(=O)OCC1=CC=CC=C1 XSKKIFJNZPNVGO-UHFFFAOYSA-N 0.000 description 2
• QZPOBBWLSGIDPY-UHFFFAOYSA-N benzyl 2-methyl-2,5-dihydropyrrole-1-carboxylate Chemical compound CC1C=CCN1C(=O)OCC1=CC=CC=C1 QZPOBBWLSGIDPY-UHFFFAOYSA-N 0.000 description 2
• MEVSPVJYDCABBN-UHFFFAOYSA-N benzyl 3-methyl-2,5-dihydropyrrole-1-carboxylate Chemical compound C1C(C)=CCN1C(=O)OCC1=CC=CC=C1 MEVSPVJYDCABBN-UHFFFAOYSA-N 0.000 description 2
• LURAHDIQJYKTPC-UHFFFAOYSA-N benzyl 6-(hydroxymethyl)-4-azabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C1C2(CO)CC2CCN1C(=O)OCC1=CC=CC=C1 LURAHDIQJYKTPC-UHFFFAOYSA-N 0.000 description 2
• 238000005574 benzylation reaction Methods 0.000 description 2
• DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
• 244000309464 bull Species 0.000 description 2
• FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 238000011097 chromatography purification Methods 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 2
• 230000018044 dehydration Effects 0.000 description 2
• 238000006297 dehydration reaction Methods 0.000 description 2
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
• NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 2
• 238000006073 displacement reaction Methods 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• QQFBQBDINHJDMN-UHFFFAOYSA-N ethyl 2-trimethylsilylacetate Chemical compound CCOC(=O)C[Si](C)(C)C QQFBQBDINHJDMN-UHFFFAOYSA-N 0.000 description 2
• SFFQYGDIFWFUAF-UHFFFAOYSA-N ethyl 3-benzyl-2,4-dioxo-3-azabicyclo[3.1.0]hexane-6-carboxylate Chemical compound CCOC(=O)C1C(C2=O)C1C(=O)N2CC1=CC=CC=C1 SFFQYGDIFWFUAF-UHFFFAOYSA-N 0.000 description 2
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 239000012467 final product Substances 0.000 description 2
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
• 229960002523 mercuric chloride Drugs 0.000 description 2
• LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 2
• 238000003328 mesylation reaction Methods 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• 150000004702 methyl esters Chemical class 0.000 description 2
• LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 2
• DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
• GBXXMZVRHDGRNM-UHFFFAOYSA-N n-(3-azabicyclo[3.1.0]hexan-1-ylmethyl)acetamide Chemical compound C1NCC2(CNC(=O)C)C1C2 GBXXMZVRHDGRNM-UHFFFAOYSA-N 0.000 description 2
• PCTLZWXRLTZUMA-UHFFFAOYSA-N n-(3-benzyl-3-azabicyclo[4.1.0]heptan-5-ylidene)hydroxylamine Chemical compound C1C2CC2C(=NO)CN1CC1=CC=CC=C1 PCTLZWXRLTZUMA-UHFFFAOYSA-N 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• NMNMAKPMFYHCNM-UHFFFAOYSA-N oxan-2-yloxymethanol Chemical group OCOC1CCCCO1 NMNMAKPMFYHCNM-UHFFFAOYSA-N 0.000 description 2
• 239000007800 oxidant agent Substances 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
• 229910000105 potassium hydride Inorganic materials 0.000 description 2
• LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 2
• SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 2
• LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
• 238000011084 recovery Methods 0.000 description 2
• 229910052703 rhodium Inorganic materials 0.000 description 2
• 239000010948 rhodium Substances 0.000 description 2
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
• 239000012047 saturated solution Substances 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• 235000017281 sodium acetate Nutrition 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 235000011006 sodium potassium tartrate Nutrition 0.000 description 2
• 239000011343 solid material Substances 0.000 description 2
• OMJNZSZOBAEAHE-UHFFFAOYSA-N tert-butyl n-(3-benzyl-3-azabicyclo[3.1.0]hexan-1-yl)carbamate Chemical compound C1C2(NC(=O)OC(C)(C)C)CC2CN1CC1=CC=CC=C1 OMJNZSZOBAEAHE-UHFFFAOYSA-N 0.000 description 2
• IBVSYGIDMGKDQZ-UHFFFAOYSA-N tert-butyl n-(4-azabicyclo[4.1.0]heptan-6-yl)carbamate Chemical compound C1CNCC2(NC(=O)OC(C)(C)C)C1C2 IBVSYGIDMGKDQZ-UHFFFAOYSA-N 0.000 description 2
• ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• 238000001149 thermolysis Methods 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
• HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
• KRZREMABTHAWQV-UHFFFAOYSA-N (3-benzyl-3-azabicyclo[3.1.0]hexan-2-yl)methanol Chemical compound OCC1C2CC2CN1CC1=CC=CC=C1 KRZREMABTHAWQV-UHFFFAOYSA-N 0.000 description 1
• WBKKROFQHWEWOP-UHFFFAOYSA-N (3-benzyl-6-methyl-3-azabicyclo[3.1.0]hexan-6-yl)methanol Chemical compound C1C2C(C)(CO)C2CN1CC1=CC=CC=C1 WBKKROFQHWEWOP-UHFFFAOYSA-N 0.000 description 1
• QOVWFJCCMIWNEO-UHFFFAOYSA-N (4-benzyl-4-azabicyclo[4.1.0]heptan-7-yl)methanol Chemical compound C1C2C(CO)C2CCN1CC1=CC=CC=C1 QOVWFJCCMIWNEO-UHFFFAOYSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• PMJHHCWVYXUKFD-SNAWJCMRSA-N (E)-1,3-pentadiene Chemical compound C\C=C\C=C PMJHHCWVYXUKFD-SNAWJCMRSA-N 0.000 description 1
• NXUCEINLRQGOSH-NSCUHMNNSA-N (e)-5-bromopent-2-ene Chemical compound C\C=C\CCBr NXUCEINLRQGOSH-NSCUHMNNSA-N 0.000 description 1
• UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
• FGNUNVVTHHKDAM-UHFFFAOYSA-N 1,2,3,6-tetrahydropyridine-5-carboxylic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CCCNC1 FGNUNVVTHHKDAM-UHFFFAOYSA-N 0.000 description 1
• ZDSOWLPYLLXDSH-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-6-fluoro-7-[6-[(2-methylpropan-2-yl)oxycarbonylamino]-4-azabicyclo[4.1.0]heptan-4-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound C1C2(NC(=O)OC(C)(C)C)CC2CCN1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1=CC=C(F)C=C1F ZDSOWLPYLLXDSH-UHFFFAOYSA-N 0.000 description 1
• STQQMFIPXJKUSK-UHFFFAOYSA-N 1-(oxan-2-yloxymethyl)-3-phenylmethoxycarbonyl-3-azabicyclo[3.1.0]hexane-6-carboxylic acid Chemical compound OC(=O)C1C2CN(C(=O)OCC=3C=CC=CC=3)CC12COC1CCCCO1 STQQMFIPXJKUSK-UHFFFAOYSA-N 0.000 description 1
• OTBHVFLPUFDBTK-UHFFFAOYSA-N 1-benzyl-2,3-dihydropyridin-6-one Chemical compound O=C1C=CCCN1CC1=CC=CC=C1 OTBHVFLPUFDBTK-UHFFFAOYSA-N 0.000 description 1
• PPNCOQHHSGMKGI-UHFFFAOYSA-N 1-cyclononyldiazonane Chemical compound C1CCCCCCCC1N1NCCCCCCC1 PPNCOQHHSGMKGI-UHFFFAOYSA-N 0.000 description 1
• KNEXGVPHPGXAGF-UHFFFAOYSA-N 1-cyclopropyl-6,7-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC(F)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 KNEXGVPHPGXAGF-UHFFFAOYSA-N 0.000 description 1
• ZCJVRBXQLONVDY-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-7-[1-[[[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]amino]methyl]-3-azabicyclo[3.1.0]hexan-3-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound C1C2(CNCCC(=O)OC(C)(C)C)CC2CN1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1CC1 ZCJVRBXQLONVDY-UHFFFAOYSA-N 0.000 description 1
• RXWYAOOKSZLRFB-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-7-[6-[(2-methylpropan-2-yl)oxycarbonylamino]-4-azabicyclo[4.1.0]heptan-4-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound C1C2(NC(=O)OC(C)(C)C)CC2CCN1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1CC1 RXWYAOOKSZLRFB-UHFFFAOYSA-N 0.000 description 1
• MUZPHFBEOYYEQH-UHFFFAOYSA-N 1-cyclopropyl-7-[1-(ethylaminomethyl)-3-azabicyclo[3.1.0]hexan-3-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1C2(CNCC)CC2CN1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1CC1 MUZPHFBEOYYEQH-UHFFFAOYSA-N 0.000 description 1
• UCOMFPMTRUMXCH-UHFFFAOYSA-N 1-methyl-2-(oxan-2-yloxy)-3-azabicyclo[4.1.0]heptan-4-one Chemical compound O1C(CCCC1)OC1C2(CC2CC(N1)=O)C UCOMFPMTRUMXCH-UHFFFAOYSA-N 0.000 description 1
• IFUAWYWONCLTQY-UHFFFAOYSA-N 1-methyl-2-(oxan-2-yloxy)bicyclo[3.1.0]hexan-3-one Chemical compound O1C(CCCC1)OC1C2(CC2CC1=O)C IFUAWYWONCLTQY-UHFFFAOYSA-N 0.000 description 1
• ZCCYVYYIAVYWFB-UHFFFAOYSA-N 1-methyl-6-(oxan-2-yloxy)-3-azabicyclo[3.1.0]hexane Chemical compound O1C(CCCC1)OC1C2CNCC12C ZCCYVYYIAVYWFB-UHFFFAOYSA-N 0.000 description 1
• UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 1
• QXYSYYCPALRMRV-UHFFFAOYSA-N 1-methylpyrrolidine-3-carbonitrile Chemical compound CN1CCC(C#N)C1 QXYSYYCPALRMRV-UHFFFAOYSA-N 0.000 description 1
• PBEWNZJEGNGCCF-UHFFFAOYSA-N 1-o-benzyl 4-o-methyl 3,6-dihydro-2h-pyridine-1,4-dicarboxylate Chemical compound C1CC(C(=O)OC)=CCN1C(=O)OCC1=CC=CC=C1 PBEWNZJEGNGCCF-UHFFFAOYSA-N 0.000 description 1
• ALCUOCVRJFRQHW-UHFFFAOYSA-N 1-phenylmethoxycarbonyl-2,5-dihydropyrrole-3-carboxylic acid Chemical compound C1C(C(=O)O)=CCN1C(=O)OCC1=CC=CC=C1 ALCUOCVRJFRQHW-UHFFFAOYSA-N 0.000 description 1
• XPERACUSRSFOFQ-UHFFFAOYSA-N 1-tert-butyl-2-methyl-3-phenylmethoxycarbonyl-3-azabicyclo[3.1.0]hexane-6,6-dicarboxylic acid Chemical compound C1C(C2(C(O)=O)C(O)=O)C2(C(C)(C)C)C(C)N1C(=O)OCC1=CC=CC=C1 XPERACUSRSFOFQ-UHFFFAOYSA-N 0.000 description 1
• LOLPWBCAZGVZLW-UHFFFAOYSA-N 2,6,6-trimethyl-5-silyloxyhept-2-en-4-one Chemical compound C(C)(C)(C)C(C(C=C(C)C)=O)O[SiH3] LOLPWBCAZGVZLW-UHFFFAOYSA-N 0.000 description 1
• HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
• DPZHKLJPVMYFCU-UHFFFAOYSA-N 2-(5-bromopyridin-2-yl)acetonitrile Chemical compound BrC1=CC=C(CC#N)N=C1 DPZHKLJPVMYFCU-UHFFFAOYSA-N 0.000 description 1
• NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 1
• AQCMZIZWHNTMBA-UHFFFAOYSA-N 2-methyl-3-azabicyclo[3.1.0]hexan-1-amine Chemical compound NC12C(NCC2C1)C AQCMZIZWHNTMBA-UHFFFAOYSA-N 0.000 description 1
• BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
• XHKFHTSQKYODAC-UHFFFAOYSA-N 2-tert-butyl-1,2-dimethyl-3-phenylmethoxycarbonyl-3-azabicyclo[3.1.0]hexane-6,6-dicarboxylic acid Chemical compound C1C(C2(C(O)=O)C(O)=O)C2(C)C(C(C)(C)C)(C)N1C(=O)OCC1=CC=CC=C1 XHKFHTSQKYODAC-UHFFFAOYSA-N 0.000 description 1
• MWTGBAURSCEGSL-UHFFFAOYSA-N 3-(benzylamino)propanenitrile Chemical compound N#CCCNCC1=CC=CC=C1 MWTGBAURSCEGSL-UHFFFAOYSA-N 0.000 description 1
• GPWDUSRNIODCOZ-UHFFFAOYSA-N 3-(oxan-2-yloxymethyl)-6-phenylhex-2-en-1-amine Chemical compound C1CCCOC1OCC(=CCN)CCCC1=CC=CC=C1 GPWDUSRNIODCOZ-UHFFFAOYSA-N 0.000 description 1
• OGVNUTOCWYRAQD-UHFFFAOYSA-N 3-[benzyl(2,3-dihydroxypropyl)amino]-4-(oxan-2-yloxy)butanenitrile Chemical compound C1CCCOC1OCC(CC#N)N(CC(O)CO)CC1=CC=CC=C1 OGVNUTOCWYRAQD-UHFFFAOYSA-N 0.000 description 1
• RQJIKIAKFMLWGV-UHFFFAOYSA-N 3-[benzyl(2,3-dihydroxypropyl)amino]propanenitrile Chemical compound OCC(O)CN(CCC#N)CC1=CC=CC=C1 RQJIKIAKFMLWGV-UHFFFAOYSA-N 0.000 description 1
• WKJGPWOGVHNOHB-UHFFFAOYSA-N 3-[benzyl(oxiran-2-ylmethyl)amino]-4-(oxan-2-yloxy)butanenitrile Chemical compound C1OC1CN(CC=1C=CC=CC=1)C(CC#N)COC1CCCCO1 WKJGPWOGVHNOHB-UHFFFAOYSA-N 0.000 description 1
• TUIHCOLESXTWCL-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexan-2-ylmethanamine Chemical compound NCC1NCC2CC12 TUIHCOLESXTWCL-UHFFFAOYSA-N 0.000 description 1
• JFUYLMCSIHJLOX-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane-2-carbonitrile Chemical compound N#CC1NCC2CC12 JFUYLMCSIHJLOX-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• FKOZOCHHBNWHEZ-UHFFFAOYSA-N 3-benzyl-1-methyl-3-azabicyclo[3.1.0]hexan-2-ol Chemical compound OC1C2(C)CC2CN1CC1=CC=CC=C1 FKOZOCHHBNWHEZ-UHFFFAOYSA-N 0.000 description 1
• JADXALLHLFMKDY-UHFFFAOYSA-N 3-benzyl-1-methyl-4-(oxan-2-yloxy)-3-azabicyclo[4.1.0]heptane Chemical compound C(C1=CC=CC=C1)N1CC2(CC2CC1OC1OCCCC1)C JADXALLHLFMKDY-UHFFFAOYSA-N 0.000 description 1
• XPJFMVGVICSMGX-UHFFFAOYSA-N 3-benzyl-1-methyl-6-(oxan-2-yloxy)-3-azabicyclo[3.1.0]hexane-2-carbonitrile Chemical compound C(C1=CC=CC=C1)N1C(C2(C(C2C1)OC1OCCCC1)C)C#N XPJFMVGVICSMGX-UHFFFAOYSA-N 0.000 description 1
• KZLNDTDKUNMYCC-UHFFFAOYSA-N 3-benzyl-2,6-dimethyl-1-(oxan-2-yloxymethyl)-3-azabicyclo[3.1.0]hexane Chemical compound CC1C2(COC3OCCCC3)C(C)C2CN1CC1=CC=CC=C1 KZLNDTDKUNMYCC-UHFFFAOYSA-N 0.000 description 1
• AMCUMGKYDRVPRE-UHFFFAOYSA-N 3-benzyl-2-methyl-3-azabicyclo[3.1.0]hexane Chemical compound CC1C2CC2CN1CC1=CC=CC=C1 AMCUMGKYDRVPRE-UHFFFAOYSA-N 0.000 description 1
• CBFGLCXLAQUBBS-UHFFFAOYSA-N 3-benzyl-3-azabicyclo[4.1.0]heptan-5-ol Chemical compound C1C2CC2C(O)CN1CC1=CC=CC=C1 CBFGLCXLAQUBBS-UHFFFAOYSA-N 0.000 description 1
• JSCMMNLMPVFMNQ-UHFFFAOYSA-N 3-benzyl-3-azabicyclo[4.1.0]heptan-5-one Chemical compound C1C2CC2C(=O)CN1CC1=CC=CC=C1 JSCMMNLMPVFMNQ-UHFFFAOYSA-N 0.000 description 1
• CUEIESMWBQBJPU-UHFFFAOYSA-N 3-benzyl-3-azabicyclo[4.1.0]heptane-6-carbonitrile Chemical compound C1CC2(C#N)CC2CN1CC1=CC=CC=C1 CUEIESMWBQBJPU-UHFFFAOYSA-N 0.000 description 1
• LKIVLOOLCUFDFY-UHFFFAOYSA-N 3-benzyl-4-ethyl-6-methyl-5-(oxan-2-yloxymethyl)-2-oxo-3-azabicyclo[3.1.0]hexane-1-carboxylic acid Chemical compound O=C1C2(C(O)=O)C(C)C2(COC2OCCCC2)C(CC)N1CC1=CC=CC=C1 LKIVLOOLCUFDFY-UHFFFAOYSA-N 0.000 description 1
• QIKAMAJHUXJUEN-UHFFFAOYSA-N 3-benzyl-5-(oxan-2-yloxymethyl)-3-azabicyclo[4.1.0]heptan-4-one Chemical compound C12CC2CN(CC=2C=CC=CC=2)C(=O)C1COC1CCCCO1 QIKAMAJHUXJUEN-UHFFFAOYSA-N 0.000 description 1
• NQVGEVDAKZVWEP-UHFFFAOYSA-N 3-benzyl-6-methyl-2-oxo-3-azabicyclo[3.1.0]hexane-1-carboxylic acid Chemical compound O=C1C2(C(O)=O)C(C)C2CN1CC1=CC=CC=C1 NQVGEVDAKZVWEP-UHFFFAOYSA-N 0.000 description 1
• YUKCUUPGXOFCSZ-UHFFFAOYSA-N 3-benzyl-6-methyl-3-azabicyclo[3.1.0]hexane Chemical compound C1C2C(C)C2CN1CC1=CC=CC=C1 YUKCUUPGXOFCSZ-UHFFFAOYSA-N 0.000 description 1
• RWIVTIKGUHUJMZ-UHFFFAOYSA-N 3-benzyl-6-methyl-3-azabicyclo[3.1.0]hexane-2-carbonitrile Chemical compound N#CC1C2C(C)C2CN1CC1=CC=CC=C1 RWIVTIKGUHUJMZ-UHFFFAOYSA-N 0.000 description 1
• FOSZCPWPTSELQP-UHFFFAOYSA-N 3-methyl-1-(oxan-2-yloxy)pent-4-en-2-ol Chemical compound C=CC(C)C(O)COC1CCCCO1 FOSZCPWPTSELQP-UHFFFAOYSA-N 0.000 description 1
• DTPFSSOXQXWKEV-UHFFFAOYSA-N 3-methyl-2,5-dihydro-1h-pyrrole Chemical compound CC1=CCNC1 DTPFSSOXQXWKEV-UHFFFAOYSA-N 0.000 description 1
• QSNAVYGCVZCQHM-UHFFFAOYSA-N 3-o-benzyl 6-o-ethyl 5-oxo-3-azabicyclo[4.1.0]heptane-3,6-dicarboxylate Chemical compound C1C(=O)C2(C(=O)OCC)CC2CN1C(=O)OCC1=CC=CC=C1 QSNAVYGCVZCQHM-UHFFFAOYSA-N 0.000 description 1
• XPSYZCWYRWHVCC-UHFFFAOYSA-N 3-o-tert-butyl 1-o-methyl propanedioate Chemical compound COC(=O)CC(=O)OC(C)(C)C XPSYZCWYRWHVCC-UHFFFAOYSA-N 0.000 description 1
• WYEPBHZLDUPIOD-UHFFFAOYSA-N 4,6-dioxoheptanoic acid Chemical compound CC(=O)CC(=O)CCC(O)=O WYEPBHZLDUPIOD-UHFFFAOYSA-N 0.000 description 1
• GNZGNWNMWPFESC-UHFFFAOYSA-N 4-[benzyl(2,3-dihydroxypropyl)amino]butanenitrile Chemical compound N#CCCCN(CC(O)CO)CC1=CC=CC=C1 GNZGNWNMWPFESC-UHFFFAOYSA-N 0.000 description 1
• KNWOHYJTPMZOHT-UHFFFAOYSA-N 4-azabicyclo[4.1.0]heptan-3-one Chemical compound C1NC(=O)CC2CC21 KNWOHYJTPMZOHT-UHFFFAOYSA-N 0.000 description 1
• OWULJVXJAZBQLL-UHFFFAOYSA-N 4-azidosulfonylbenzoic acid Chemical compound OC(=O)C1=CC=C(S(=O)(=O)N=[N+]=[N-])C=C1 OWULJVXJAZBQLL-UHFFFAOYSA-N 0.000 description 1
• JJULERZCXKBOGM-UHFFFAOYSA-N 4-benzyl-1-(oxan-2-yloxymethyl)-5-oxo-4-azabicyclo[4.1.0]heptane-6-carboxylic acid Chemical compound C1CN(CC=2C=CC=CC=2)C(=O)C2(C(=O)O)CC21COC1CCCCO1 JJULERZCXKBOGM-UHFFFAOYSA-N 0.000 description 1
• KRSQVCPJDBPHGV-UHFFFAOYSA-N 4-benzyl-1-methyl-7-(oxan-2-yloxymethyl)-5-oxo-4-azabicyclo[4.1.0]heptane-6-carboxylic acid Chemical compound O=C1C(C(O)=O)(C2COC3OCCCC3)C2(C)CCN1CC1=CC=CC=C1 KRSQVCPJDBPHGV-UHFFFAOYSA-N 0.000 description 1
• FEVHVVFCGZVFEH-UHFFFAOYSA-N 4-benzyl-4-azabicyclo[4.1.0]heptan-3-one Chemical compound O=C1CC2CC2CN1CC1=CC=CC=C1 FEVHVVFCGZVFEH-UHFFFAOYSA-N 0.000 description 1
• AWRVRPHELFNBNU-UHFFFAOYSA-N 4-benzyl-4-azabicyclo[4.1.0]heptane Chemical compound C1CC2CC2CN1CC1=CC=CC=C1 AWRVRPHELFNBNU-UHFFFAOYSA-N 0.000 description 1
• UPCDJMVPZPHLHI-UHFFFAOYSA-N 4-benzyl-6-methyl-5-(oxan-2-yloxy)-4-azabicyclo[4.1.0]heptane Chemical compound C1CCCOC1OC1C2(C)CC2CCN1CC1=CC=CC=C1 UPCDJMVPZPHLHI-UHFFFAOYSA-N 0.000 description 1
• HOTAEXPIKKKYKU-UHFFFAOYSA-N 4-benzyl-7-methyl-1-(oxan-2-yloxymethyl)-5-oxo-4-azabicyclo[4.1.0]heptane-6-carboxylic acid Chemical compound C1CN(CC=2C=CC=CC=2)C(=O)C2(C(O)=O)C(C)C21COC1CCCCO1 HOTAEXPIKKKYKU-UHFFFAOYSA-N 0.000 description 1
• QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
• CQPGDDAKTTWVDD-UHFFFAOYSA-N 4-bromobutanenitrile Chemical compound BrCCCC#N CQPGDDAKTTWVDD-UHFFFAOYSA-N 0.000 description 1
• CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 1
• PTSCVSKFNKCJLD-UHFFFAOYSA-N 4-methyl-6-(oxan-2-yloxymethyl)-3-azabicyclo[3.1.0]hexane-2-carbonitrile Chemical compound C12C(C)NC(C#N)C2C1COC1CCCCO1 PTSCVSKFNKCJLD-UHFFFAOYSA-N 0.000 description 1
• VFWGARUZRPAUQY-UHFFFAOYSA-N 4-o-benzyl 7-o-ethyl 4-azabicyclo[4.1.0]heptane-4,7-dicarboxylate Chemical compound C1C2C(C(=O)OCC)C2CCN1C(=O)OCC1=CC=CC=C1 VFWGARUZRPAUQY-UHFFFAOYSA-N 0.000 description 1
• QCNXZRJPMLVXAH-UHFFFAOYSA-N 4-o-benzyl 7-o-ethyl 5-(oxan-2-yloxymethyl)-4-azabicyclo[4.1.0]heptane-4,7-dicarboxylate Chemical compound C12C(C(=O)OCC)C2CCN(C(=O)OCC=2C=CC=CC=2)C1COC1CCCCO1 QCNXZRJPMLVXAH-UHFFFAOYSA-N 0.000 description 1
• ILNJBIQQAIIMEY-UHFFFAOYSA-N 4-oxo-1h-quinoline-3-carboxylic acid Chemical class C1=CC=CC2=C(O)C(C(=O)O)=CN=C21 ILNJBIQQAIIMEY-UHFFFAOYSA-N 0.000 description 1
• ZMYPZFFORMZOLN-UHFFFAOYSA-N 5-(oxan-2-yloxymethyl)-3-phenylmethoxycarbonyl-3-azabicyclo[4.1.0]heptane-7-carboxylic acid Chemical compound C12C(C(=O)O)C2CN(C(=O)OCC=2C=CC=CC=2)CC1COC1CCCCO1 ZMYPZFFORMZOLN-UHFFFAOYSA-N 0.000 description 1
• OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
• IZOQMUVIDMLRDC-UHFFFAOYSA-N 5-aceto valeric acid Chemical compound CC(=O)CCCCC(O)=O IZOQMUVIDMLRDC-UHFFFAOYSA-N 0.000 description 1
• PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
• QRDSDKAGXMWBID-UHFFFAOYSA-N 5-azabicyclo[3.1.0]hexane Chemical compound C1CCN2CC21 QRDSDKAGXMWBID-UHFFFAOYSA-N 0.000 description 1
• KSBLVIUMTJQOIH-UHFFFAOYSA-N 5-methyl-4-(oxan-2-yloxymethyl)-3-phenylmethoxycarbonyl-3-azabicyclo[4.1.0]heptane-7-carboxylic acid Chemical compound CC1C(C2C(O)=O)C2CN(C(=O)OCC=2C=CC=CC=2)C1COC1CCCCO1 KSBLVIUMTJQOIH-UHFFFAOYSA-N 0.000 description 1
• MAPXTKXCQKLXMA-UHFFFAOYSA-N 6-(oxan-2-yloxymethyl)-4-phenylmethoxycarbonyl-4-azabicyclo[4.1.0]heptane-7-carboxylic acid Chemical compound OC(=O)C1C2CCN(C(=O)OCC=3C=CC=CC=3)CC12COC1CCCCO1 MAPXTKXCQKLXMA-UHFFFAOYSA-N 0.000 description 1
• JWUYNZCNKGYPSY-UHFFFAOYSA-N 7-(1-acetamido-3-azabicyclo[3.1.0]hexan-3-yl)-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C1C2(NC(=O)C)CC2CN1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=NC=1N2C1=CC=C(F)C=C1F JWUYNZCNKGYPSY-UHFFFAOYSA-N 0.000 description 1
• POAYQQBMYUJVMG-UHFFFAOYSA-N 7-(6-amino-4-azabicyclo[4.1.0]heptan-4-yl)-1-(2,4-difluorophenyl)-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1C2(N)CC2CCN1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1=CC=C(F)C=C1F POAYQQBMYUJVMG-UHFFFAOYSA-N 0.000 description 1
• HOPNGBWLZGKNCH-UHFFFAOYSA-N 7-(6-amino-4-azabicyclo[4.1.0]heptan-4-yl)-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1C2(N)CC2CCN1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1CC1 HOPNGBWLZGKNCH-UHFFFAOYSA-N 0.000 description 1
• OXNZWNNMJBOZQO-UHFFFAOYSA-N 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C12=NC(Cl)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 OXNZWNNMJBOZQO-UHFFFAOYSA-N 0.000 description 1
• WPFWFBYDDNRVRX-UHFFFAOYSA-N 7-methyl-4-(oxan-2-yloxymethyl)-3-phenylmethoxycarbonyl-3-azabicyclo[4.1.0]heptane-5-carboxylic acid Chemical compound OC(=O)C1C2C(C)C2CN(C(=O)OCC=2C=CC=CC=2)C1COC1CCCCO1 WPFWFBYDDNRVRX-UHFFFAOYSA-N 0.000 description 1
• 229910000497 Amalgam Inorganic materials 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
• 238000006237 Beckmann rearrangement reaction Methods 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
• 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
• 238000006809 Jones oxidation reaction Methods 0.000 description 1
• 239000003810 Jones reagent Substances 0.000 description 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
• RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
• FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
• UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
• UCUNFLYVYCGDHP-BYPYZUCNSA-N L-methionine sulfone Chemical compound CS(=O)(=O)CC[C@H](N)C(O)=O UCUNFLYVYCGDHP-BYPYZUCNSA-N 0.000 description 1
• SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• CSAYVSRENVQAPV-UHFFFAOYSA-N N1=CC=CC2=CC=CC=C21.C1=CC=C2ONC(C(=O)O)=CC2=C1 Chemical class N1=CC=CC2=CC=CC=C21.C1=CC=C2ONC(C(=O)O)=CC2=C1 CSAYVSRENVQAPV-UHFFFAOYSA-N 0.000 description 1
• RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
• QPFYXYFORQJZEC-FOCLMDBBSA-N Phenazopyridine Chemical compound NC1=NC(N)=CC=C1\N=N\C1=CC=CC=C1 QPFYXYFORQJZEC-FOCLMDBBSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 238000007295 Wittig olefination reaction Methods 0.000 description 1
• 238000007239 Wittig reaction Methods 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• WKTADPTYXPWYNH-UHFFFAOYSA-N [4-benzyl-2-(oxan-2-yloxymethyl)-4-azabicyclo[4.1.0]heptan-6-yl]methanol Chemical compound C1N(CC=2C=CC=CC=2)CC2(CO)CC2C1COC1CCCCO1 WKTADPTYXPWYNH-UHFFFAOYSA-N 0.000 description 1
• JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 1
• JOBBRIRILCAFIA-UHFFFAOYSA-N ac1l9md0 Chemical compound O.O.O.O.O.O.O.O.O JOBBRIRILCAFIA-UHFFFAOYSA-N 0.000 description 1
• 150000003869 acetamides Chemical class 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 238000005903 acid hydrolysis reaction Methods 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 125000003158 alcohol group Chemical group 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
• 229910001863 barium hydroxide Inorganic materials 0.000 description 1
• ATKJLMWDXASAJA-UHFFFAOYSA-N benzenesulfonylsulfanylbenzene Chemical compound C=1C=CC=CC=1S(=O)(=O)SC1=CC=CC=C1 ATKJLMWDXASAJA-UHFFFAOYSA-N 0.000 description 1
• WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
• IJCBUTCLNYRIPJ-UHFFFAOYSA-N benzyl 2,3-dimethyl-2,5-dihydropyrrole-1-carboxylate Chemical compound C1C=C(C)C(C)N1C(=O)OCC1=CC=CC=C1 IJCBUTCLNYRIPJ-UHFFFAOYSA-N 0.000 description 1
• LXJKVSORUFXHGT-UHFFFAOYSA-N benzyl 2-methyl-6-(oxan-2-yloxymethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C12CN(C(=O)OCC=3C=CC=CC=3)C(C)C2C1COC1CCCCO1 LXJKVSORUFXHGT-UHFFFAOYSA-N 0.000 description 1
• PBQBEIRQKVIFRT-UHFFFAOYSA-N benzyl 3-(oxan-2-yloxymethyl)-2,5-dihydropyrrole-1-carboxylate Chemical compound C1C=C(COC2OCCCC2)CN1C(=O)OCC1=CC=CC=C1 PBQBEIRQKVIFRT-UHFFFAOYSA-N 0.000 description 1
• LMHWEUQNJRXMCD-UHFFFAOYSA-N benzyl 3-oxopyrrolidine-1-carboxylate Chemical compound C1CC(=O)CN1C(=O)OCC1=CC=CC=C1 LMHWEUQNJRXMCD-UHFFFAOYSA-N 0.000 description 1
• DJQBVWZYUPMSQG-UHFFFAOYSA-N benzyl 6,6-dibromo-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1C2C(Br)(Br)C2CN1C(=O)OCC1=CC=CC=C1 DJQBVWZYUPMSQG-UHFFFAOYSA-N 0.000 description 1
• KWADVHWEIMWPJG-UHFFFAOYSA-N benzyl 6-(hydroxymethyl)-2-(oxan-2-yloxymethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)N1CCC2(CO)CC2C1COC1CCCCO1 KWADVHWEIMWPJG-UHFFFAOYSA-N 0.000 description 1
• GLUCCSRTDLECBE-UHFFFAOYSA-N benzyl 6-(hydroxymethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate Chemical compound C1CC2(CO)CC2CN1C(=O)OCC1=CC=CC=C1 GLUCCSRTDLECBE-UHFFFAOYSA-N 0.000 description 1
• NPRPWLGPNCNXIO-UHFFFAOYSA-N benzyl 6-(hydroxymethyl)-6-methyl-1-(oxan-2-yloxymethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound OCC1(C)C2CN(C(=O)OCC=3C=CC=CC=3)CC12COC1CCCCO1 NPRPWLGPNCNXIO-UHFFFAOYSA-N 0.000 description 1
• BQEIVXAYKPKEKT-UHFFFAOYSA-N benzyl 6-[(2-methylpropan-2-yl)oxycarbonylamino]-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1C2C(NC(=O)OC(C)(C)C)C2CN1C(=O)OCC1=CC=CC=C1 BQEIVXAYKPKEKT-UHFFFAOYSA-N 0.000 description 1
• KDPGLXPHKYEBKP-UHFFFAOYSA-N benzyl 7,7-dibromo-5-(oxan-2-yloxymethyl)-4-azabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C12C(Br)(Br)C2CCN(C(=O)OCC=2C=CC=CC=2)C1COC1CCCCO1 KDPGLXPHKYEBKP-UHFFFAOYSA-N 0.000 description 1
• IKLZVHPKIBTSLZ-UHFFFAOYSA-N benzyl 7-bromo-5-hydroxy-7-methyl-3-azabicyclo[4.1.0]heptane-3-carboxylate Chemical compound C1C(O)C2C(C)(Br)C2CN1C(=O)OCC1=CC=CC=C1 IKLZVHPKIBTSLZ-UHFFFAOYSA-N 0.000 description 1
• LZSGNEZLQOXOFU-UHFFFAOYSA-N benzyl 7-methyl-4-(oxan-2-yloxymethyl)-5-oxo-3-azabicyclo[4.1.0]heptane-3-carboxylate Chemical compound O=C1C2C(C)C2CN(C(=O)OCC=2C=CC=CC=2)C1COC1CCCCO1 LZSGNEZLQOXOFU-UHFFFAOYSA-N 0.000 description 1
• HKBVZRNROJEWIP-UHFFFAOYSA-N benzyl 7-methyl-5-oxo-3-azabicyclo[4.1.0]heptane-3-carboxylate Chemical compound C1C(=O)C2C(C)C2CN1C(=O)OCC1=CC=CC=C1 HKBVZRNROJEWIP-UHFFFAOYSA-N 0.000 description 1
• 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• WQQZKEFUOHKGII-UHFFFAOYSA-N bicyclo[3.1.0]hexan-3-one Chemical compound C1C(=O)CC2CC21 WQQZKEFUOHKGII-UHFFFAOYSA-N 0.000 description 1
• 229950005228 bromoform Drugs 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 0.000 description 1
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 229960002173 citrulline Drugs 0.000 description 1
• 235000013477 citrulline Nutrition 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000000039 congener Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• RLWFMZKPPHHHCB-UHFFFAOYSA-N cyclopropane-1,2-dicarboxylate;hydron Chemical compound OC(=O)C1CC1C(O)=O RLWFMZKPPHHHCB-UHFFFAOYSA-N 0.000 description 1
• YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 150000008049 diazo compounds Chemical class 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 150000002009 diols Chemical class 0.000 description 1
• ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical group CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 1
• PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
• 239000003651 drinking water Substances 0.000 description 1
• 235000020188 drinking water Nutrition 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
• 238000010931 ester hydrolysis Methods 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
• ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
• DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
• YKWNUSJLICDQEO-UHFFFAOYSA-N ethoxyethane;propan-2-ol Chemical compound CC(C)O.CCOCC YKWNUSJLICDQEO-UHFFFAOYSA-N 0.000 description 1
• UCHJWSNOVHXTKU-UHFFFAOYSA-N ethyl 1-(2,4-difluorophenyl)-6,7-difluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=CC(F)=C(F)C=C2C(=O)C(C(=O)OCC)=CN1C1=CC=C(F)C=C1F UCHJWSNOVHXTKU-UHFFFAOYSA-N 0.000 description 1
• RTDJLOFWEDKRPR-UHFFFAOYSA-N ethyl 4-benzyl-5-oxo-4-azabicyclo[4.1.0]heptane-7-carboxylate Chemical compound O=C1C2C(C(=O)OCC)C2CCN1CC1=CC=CC=C1 RTDJLOFWEDKRPR-UHFFFAOYSA-N 0.000 description 1
• OHLRLMWUFVDREV-UHFFFAOYSA-N ethyl 4-chloro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)CCl OHLRLMWUFVDREV-UHFFFAOYSA-N 0.000 description 1
• NNQYFBSGBOKZKP-UHFFFAOYSA-N ethylidene(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC)C1=CC=CC=C1 NNQYFBSGBOKZKP-UHFFFAOYSA-N 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
• 230000022244 formylation Effects 0.000 description 1
• 238000006170 formylation reaction Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 238000007306 functionalization reaction Methods 0.000 description 1
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
• 229960002591 hydroxyproline Drugs 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical compound ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
• XMYQHJDBLRZMLW-UHFFFAOYSA-N methanolamine Chemical compound NCO XMYQHJDBLRZMLW-UHFFFAOYSA-N 0.000 description 1
• SJFNDMHZXCUXSA-UHFFFAOYSA-M methoxymethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SJFNDMHZXCUXSA-UHFFFAOYSA-M 0.000 description 1
• MQICXGHTFDWPFX-UHFFFAOYSA-N methyl 1-methyl-3-thiophen-2-ylpyrrolidine-3-carboxylate Chemical compound COC(=O)C1(CN(CC1)C)C=1SC=CC1 MQICXGHTFDWPFX-UHFFFAOYSA-N 0.000 description 1
• GJKXAWWEZQIKST-UHFFFAOYSA-N methyl 2-(benzylamino)-3-(oxan-2-yloxy)propanoate Chemical compound C=1C=CC=CC=1CNC(C(=O)OC)COC1CCCCO1 GJKXAWWEZQIKST-UHFFFAOYSA-N 0.000 description 1
• UAWVZBDVSNLPDT-UHFFFAOYSA-N methyl 2-(benzylamino)acetate Chemical compound COC(=O)CNCC1=CC=CC=C1 UAWVZBDVSNLPDT-UHFFFAOYSA-N 0.000 description 1
• HIVDOHPKFIBYPZ-UHFFFAOYSA-N methyl 2-(benzylamino)propanoate Chemical compound COC(=O)C(C)NCC1=CC=CC=C1 HIVDOHPKFIBYPZ-UHFFFAOYSA-N 0.000 description 1
• GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 1
• 125000004492 methyl ester group Chemical group 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
• IJTCVRCODZRTAE-UHFFFAOYSA-N n-[(3-benzyl-3-azabicyclo[3.1.0]hexan-1-yl)methyl]acetamide Chemical compound C1C2(CNC(=O)C)CC2CN1CC1=CC=CC=C1 IJTCVRCODZRTAE-UHFFFAOYSA-N 0.000 description 1
• AILMJHHPMIRQHV-UHFFFAOYSA-N n-[(3-benzyl-3-azabicyclo[3.1.0]hexan-1-yl)methyl]ethanamine Chemical compound C1C2(CNCC)CC2CN1CC1=CC=CC=C1 AILMJHHPMIRQHV-UHFFFAOYSA-N 0.000 description 1
• ROTSPSKRULUAJM-UHFFFAOYSA-N n-benzyl-2-(oxan-2-yloxymethyl)but-3-en-1-amine Chemical compound C1CCCOC1OCC(C=C)CNCC1=CC=CC=C1 ROTSPSKRULUAJM-UHFFFAOYSA-N 0.000 description 1
• WTHNDBATJRQTQC-UHFFFAOYSA-N n-benzyl-3-(oxan-2-yloxymethyl)but-3-en-1-amine Chemical compound C1CCCOC1OCC(=C)CCNCC1=CC=CC=C1 WTHNDBATJRQTQC-UHFFFAOYSA-N 0.000 description 1
• FILNVDDHDRXIEA-UHFFFAOYSA-N n-benzylpent-3-en-1-amine Chemical compound CC=CCCNCC1=CC=CC=C1 FILNVDDHDRXIEA-UHFFFAOYSA-N 0.000 description 1
• BNYNJIKGRPHFAM-UHFFFAOYSA-N n-heptylidenehydroxylamine Chemical compound CCCCCCC=NO BNYNJIKGRPHFAM-UHFFFAOYSA-N 0.000 description 1
• 125000002560 nitrile group Chemical group 0.000 description 1
• 238000010641 nitrile hydrolysis reaction Methods 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• 239000012285 osmium tetroxide Substances 0.000 description 1
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• ZHZCYWWNFQUZOR-UHFFFAOYSA-N pent-4-en-2-ol Chemical compound CC(O)CC=C ZHZCYWWNFQUZOR-UHFFFAOYSA-N 0.000 description 1
• DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
• PLHSKXBFZPAQOD-UHFFFAOYSA-N phenyl(tribromomethyl)mercury Chemical compound BrC(Br)(Br)[Hg]C1=CC=CC=C1 PLHSKXBFZPAQOD-UHFFFAOYSA-N 0.000 description 1
• XNQULTQRGBXLIA-UHFFFAOYSA-O phosphonic anhydride Chemical compound O[P+](O)=O XNQULTQRGBXLIA-UHFFFAOYSA-O 0.000 description 1
• PMJHHCWVYXUKFD-UHFFFAOYSA-N piperylene Natural products CC=CC=C PMJHHCWVYXUKFD-UHFFFAOYSA-N 0.000 description 1
• 229920001184 polypeptide Chemical group 0.000 description 1
• 108090000765 processed proteins & peptides Chemical group 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• WFGIWHQFOVSHAU-UHFFFAOYSA-N propan-2-yl n-(3-benzyl-3-azabicyclo[3.1.0]hexan-1-yl)carbamate Chemical compound C1C2(NC(=O)OC(C)C)CC2CN1CC1=CC=CC=C1 WFGIWHQFOVSHAU-UHFFFAOYSA-N 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• DKORSYDQYFVQNS-UHFFFAOYSA-N propyl methanesulfonate Chemical compound CCCOS(C)(=O)=O DKORSYDQYFVQNS-UHFFFAOYSA-N 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
• ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
• 229940070891 pyridium Drugs 0.000 description 1
• ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 150000003333 secondary alcohols Chemical class 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 1
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
• 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
• UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
• 229960002218 sodium chlorite Drugs 0.000 description 1
• 239000001476 sodium potassium tartrate Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
• QHSPZGZEUDEIQM-AATRIKPKSA-N tert-butyl (e)-but-2-enoate Chemical compound C\C=C\C(=O)OC(C)(C)C QHSPZGZEUDEIQM-AATRIKPKSA-N 0.000 description 1
• IGHZMPVJPRKIGZ-UHFFFAOYSA-N tert-butyl 3-(3-azabicyclo[3.1.0]hexan-1-ylmethylamino)propanoate Chemical compound C1NCC2(CNCCC(=O)OC(C)(C)C)C1C2 IGHZMPVJPRKIGZ-UHFFFAOYSA-N 0.000 description 1
• NEMLWDBDTQZQDK-UHFFFAOYSA-N tert-butyl n-(2-methyl-3-azabicyclo[3.1.0]hexan-1-yl)carbamate Chemical compound CC1NCC2CC12NC(=O)OC(C)(C)C NEMLWDBDTQZQDK-UHFFFAOYSA-N 0.000 description 1
• IJHTZGBRXSYOMG-UHFFFAOYSA-N tert-butyl n-(3-azabicyclo[3.1.0]hexan-1-yl)carbamate Chemical compound C1NCC2(NC(=O)OC(C)(C)C)C1C2 IJHTZGBRXSYOMG-UHFFFAOYSA-N 0.000 description 1
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• NDLIRBZKZSDGSO-UHFFFAOYSA-N tosyl azide Chemical compound CC1=CC=C(S(=O)(=O)[N-][N+]#N)C=C1 NDLIRBZKZSDGSO-UHFFFAOYSA-N 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
• LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
• 229910052721 tungsten Inorganic materials 0.000 description 1
• 239000003039 volatile agent Substances 0.000 description 1
• 239000002023 wood Substances 0.000 description 1
• 229910052727 yttrium Inorganic materials 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1