JP7311944B2 - 二環性含窒素複素環誘導体を含有する医薬組成物 - Google Patents

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Publication number

JP7311944B2

JP7311944B2 JP2019076854A JP2019076854A JP7311944B2 JP 7311944 B2 JP7311944 B2 JP 7311944B2 JP 2019076854 A JP2019076854 A JP 2019076854A JP 2019076854 A JP2019076854 A JP 2019076854A JP 7311944 B2 JP7311944 B2 JP 7311944B2

Authority

JP

Japan

Prior art keywords

substituted

unsubstituted

group

aromatic heterocyclic

groups selected

Prior art date

2018-04-16

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• 239000008194 pharmaceutical composition Substances 0.000 title description 57
• 125000001424 substituent group Chemical group 0.000 claims description 622
• 150000001875 compounds Chemical class 0.000 claims description 415
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 227
• 125000000217 alkyl group Chemical group 0.000 claims description 211
• 150000003839 salts Chemical class 0.000 claims description 211
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 200
• 229910052736 halogen Inorganic materials 0.000 claims description 173
• 150000002367 halogens Chemical class 0.000 claims description 171
• 125000003118 aryl group Chemical group 0.000 claims description 166
• 125000002837 carbocyclic group Chemical group 0.000 claims description 136
• 125000003545 alkoxy group Chemical group 0.000 claims description 118
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 80
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 70
• 125000003282 alkyl amino group Chemical group 0.000 claims description 63
• 125000003342 alkenyl group Chemical group 0.000 claims description 61
• 125000000304 alkynyl group Chemical group 0.000 claims description 54
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 47
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 41
• 125000005133 alkynyloxy group Chemical group 0.000 claims description 39
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 37
• 125000006319 alkynyl amino group Chemical group 0.000 claims description 29
• 125000006323 alkenyl amino group Chemical group 0.000 claims description 27
• 208000002193 Pain Diseases 0.000 claims description 22
• 230000036407 pain Effects 0.000 claims description 20
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
• 239000003795 chemical substances by application Substances 0.000 claims description 12
• 238000002360 preparation method Methods 0.000 claims description 12
• 230000002401 inhibitory effect Effects 0.000 claims description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001041 indolyl group Chemical group 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
• 230000001225 therapeutic effect Effects 0.000 claims description 3
• 125000005412 pyrazyl group Chemical group 0.000 claims description 2
• 230000003449 preventive effect Effects 0.000 claims 1
• -1 ATP Chemical class 0.000 description 419
• 229910052757 nitrogen Inorganic materials 0.000 description 102
• 125000004433 nitrogen atom Chemical group N* 0.000 description 97
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
• 239000002904 solvent Substances 0.000 description 76
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 75
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 66
• 238000000034 method Methods 0.000 description 66
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 64
• 125000003277 amino group Chemical group 0.000 description 62
• 125000004414 alkyl thio group Chemical group 0.000 description 61
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
• 239000000243 solution Substances 0.000 description 59
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
• 238000006243 chemical reaction Methods 0.000 description 50
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 49
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 48
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 47
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 46
• 230000002829 reductive effect Effects 0.000 description 43
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
• 239000000203 mixture Substances 0.000 description 39
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 38
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 36
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 34
• 238000007796 conventional method Methods 0.000 description 34
• 238000004440 column chromatography Methods 0.000 description 33
• 238000001953 recrystallisation Methods 0.000 description 33
• 238000004458 analytical method Methods 0.000 description 32
• 229910052751 metal Inorganic materials 0.000 description 32
• 239000002184 metal Substances 0.000 description 32
• 238000010898 silica gel chromatography Methods 0.000 description 32
• 125000005115 alkyl carbamoyl group Chemical group 0.000 description 31
• 239000012044 organic layer Substances 0.000 description 31
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
• 230000014759 maintenance of location Effects 0.000 description 30
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 28
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 28
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 27
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 27
• 125000005153 alkyl sulfamoyl group Chemical group 0.000 description 27
• 239000002585 base Substances 0.000 description 26
• 230000008569 process Effects 0.000 description 26
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 25
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 25
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 24
• 125000004430 oxygen atom Chemical group O* 0.000 description 24
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
• 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 24
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 22
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 22
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 21
• 102100037602 P2X purinoceptor 7 Human genes 0.000 description 21
• 229910052799 carbon Inorganic materials 0.000 description 21
• 239000007810 chemical reaction solvent Substances 0.000 description 21
• 150000002170 ethers Chemical class 0.000 description 21
• 125000002950 monocyclic group Chemical group 0.000 description 21
• 230000035484 reaction time Effects 0.000 description 21
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 20
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
• 125000005090 alkenylcarbonyl group Chemical group 0.000 description 20
• 125000005087 alkynylcarbonyl group Chemical group 0.000 description 20
• 150000004945 aromatic hydrocarbons Chemical group 0.000 description 20
• 239000012299 nitrogen atmosphere Substances 0.000 description 20
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 20
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 20
• 229910052717 sulfur Inorganic materials 0.000 description 20
• 239000008096 xylene Substances 0.000 description 20
• 101710189965 P2X purinoceptor 7 Proteins 0.000 description 19
• 125000005092 alkenyloxycarbonyl group Chemical group 0.000 description 19
• 125000005225 alkynyloxycarbonyl group Chemical group 0.000 description 19
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 19
• 125000004432 carbon atom Chemical group C* 0.000 description 19
• 125000001188 haloalkyl group Chemical group 0.000 description 19
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 18
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 18
• 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 18
• 239000010410 layer Substances 0.000 description 18
• 229910052760 oxygen Inorganic materials 0.000 description 18
• 125000005137 alkenylsulfonyl group Chemical group 0.000 description 17
• 125000005139 alkynylsulfonyl group Chemical group 0.000 description 17
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 16
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 16
• 239000012043 crude product Substances 0.000 description 16
• 125000006413 ring segment Chemical group 0.000 description 16
• 229920006395 saturated elastomer Polymers 0.000 description 16
• 229930195734 saturated hydrocarbon Natural products 0.000 description 16
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 15
• FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 15
• 125000002619 bicyclic group Chemical group 0.000 description 15
• 125000000623 heterocyclic group Chemical group 0.000 description 15
• 239000012312 sodium hydride Substances 0.000 description 15
• 229910000104 sodium hydride Inorganic materials 0.000 description 15
• 238000005160 1H NMR spectroscopy Methods 0.000 description 14
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 14
• 230000015572 biosynthetic process Effects 0.000 description 14
• 150000001721 carbon Chemical group 0.000 description 14
• 238000001816 cooling Methods 0.000 description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
• 238000001308 synthesis method Methods 0.000 description 14
• 238000003786 synthesis reaction Methods 0.000 description 14
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
• 125000005091 alkenylcarbonylamino group Chemical group 0.000 description 13
• 125000005193 alkenylcarbonyloxy group Chemical group 0.000 description 13
• 125000005088 alkynylcarbonylamino group Chemical group 0.000 description 13
• 125000005198 alkynylcarbonyloxy group Chemical group 0.000 description 13
• 125000003396 thiol group Chemical group [H]S* 0.000 description 13
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 12
• 229910000024 caesium carbonate Inorganic materials 0.000 description 12
• 125000004122 cyclic group Chemical group 0.000 description 12
• 201000010099 disease Diseases 0.000 description 12
• 229910000027 potassium carbonate Inorganic materials 0.000 description 12
• MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 11
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 11
• 235000019270 ammonium chloride Nutrition 0.000 description 11
• 238000005194 fractionation Methods 0.000 description 11
• 239000007864 aqueous solution Substances 0.000 description 10
• 125000004429 atom Chemical group 0.000 description 10
• 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 10
• 150000008282 halocarbons Chemical class 0.000 description 10
• 229910052740 iodine Inorganic materials 0.000 description 10
• 239000011630 iodine Substances 0.000 description 10
• 229910000029 sodium carbonate Inorganic materials 0.000 description 10
• CXNIUSPIQKWYAI-UHFFFAOYSA-N 4,5-bis(diphenylphosphino)-9,9-dimethyl-xanthene Substances C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 9
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 9
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 9
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 9
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 9
• 239000003054 catalyst Substances 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 125000001072 heteroaryl group Chemical group 0.000 description 9
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
• 150000004703 alkoxides Chemical class 0.000 description 8
• 229910000000 metal hydroxide Inorganic materials 0.000 description 8
• 150000004692 metal hydroxides Chemical class 0.000 description 8
• 230000003287 optical effect Effects 0.000 description 8
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• 229940002612 prodrug Drugs 0.000 description 8
• 239000000651 prodrug Substances 0.000 description 8
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• 235000019798 tripotassium phosphate Nutrition 0.000 description 8
• 238000000825 ultraviolet detection Methods 0.000 description 8
• 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 7
• 208000024827 Alzheimer disease Diseases 0.000 description 7
• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 7
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• 239000002253 acid Substances 0.000 description 7
• 230000001154 acute effect Effects 0.000 description 7
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 7
• 235000019253 formic acid Nutrition 0.000 description 7
• 125000004438 haloalkoxy group Chemical group 0.000 description 7
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• 229910000103 lithium hydride Inorganic materials 0.000 description 7
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• 201000008482 osteoarthritis Diseases 0.000 description 7
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• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
• ZUVPLKVDZNDZCM-UHFFFAOYSA-N 3-chloro-2-methylaniline Chemical compound CC1=C(N)C=CC=C1Cl ZUVPLKVDZNDZCM-UHFFFAOYSA-N 0.000 description 6
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• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 6
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• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 6
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• 150000001298 alcohols Chemical class 0.000 description 6
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 6
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• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
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• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 6
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