CS160591A3 - Quinazoline derivatives, process for their manufacture and their application as medicaments - Google Patents

Info

Publication number

CS160591A3

CS160591A3 CS911605A CS160591A CS160591A3 CS 160591 A3 CS160591 A3 CS 160591A3 CS 911605 A CS911605 A CS 911605A CS 160591 A CS160591 A CS 160591A CS 160591 A3 CS160591 A3 CS 160591A3

Authority

CS

Czechoslovakia

Prior art keywords

group

carbon atoms

amino

methyl

formula

Prior art date

1990-05-30

Links

• Espacenet
• Global Dossier
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• 238000000034 method Methods 0.000 title claims description 69
• 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title claims description 53
• 239000003814 drug Substances 0.000 title claims description 8
• 238000004519 manufacturing process Methods 0.000 title description 3
• -1 hydroxymethylene group Chemical group 0.000 claims description 415
• 125000004432 carbon atom Chemical group C* 0.000 claims description 214
• 125000001424 substituent group Chemical group 0.000 claims description 87
• 150000001875 compounds Chemical class 0.000 claims description 85
• 125000003118 aryl group Chemical group 0.000 claims description 75
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 67
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 59
• 150000003839 salts Chemical class 0.000 claims description 44
• 125000006239 protecting group Chemical group 0.000 claims description 43
• 125000000217 alkyl group Chemical group 0.000 claims description 39
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 38
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 35
• 229910052786 argon Inorganic materials 0.000 claims description 34
• 239000002253 acid Substances 0.000 claims description 32
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
• 229910052727 yttrium Inorganic materials 0.000 claims description 32
• 125000003277 amino group Chemical group 0.000 claims description 31
• 125000001072 heteroaryl group Chemical group 0.000 claims description 31
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 30
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 26
• 238000002360 preparation method Methods 0.000 claims description 25
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 24
• 125000003545 alkoxy group Chemical group 0.000 claims description 23
• 125000003282 alkyl amino group Chemical group 0.000 claims description 22
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 19
• 230000000259 anti-tumor effect Effects 0.000 claims description 18
• 238000006243 chemical reaction Methods 0.000 claims description 18
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 17
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
• 229910052801 chlorine Inorganic materials 0.000 claims description 16
• 125000001153 fluoro group Chemical group F* 0.000 claims description 16
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 16
• 229910052757 nitrogen Inorganic materials 0.000 claims description 16
• 125000002947 alkylene group Chemical group 0.000 claims description 15
• 125000005110 aryl thio group Chemical group 0.000 claims description 15
• 125000005843 halogen group Chemical group 0.000 claims description 15
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 13
• 125000001188 haloalkyl group Chemical group 0.000 claims description 13
• 125000005368 heteroarylthio group Chemical group 0.000 claims description 13
• 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 12
• 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 11
• 125000004414 alkyl thio group Chemical group 0.000 claims description 11
• 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 10
• 125000004429 atom Chemical group 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 10
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 10
• 125000005449 2-fluoro-1,4-phenylene group Chemical group [H]C1=C([*:2])C([H])=C(F)C([*:1])=C1[H] 0.000 claims description 9
• 241001465754 Metazoa Species 0.000 claims description 9
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 9
• 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 9
• 150000002367 halogens Chemical class 0.000 claims description 8
• 229910052739 hydrogen Inorganic materials 0.000 claims description 8
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 8
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 239000001257 hydrogen Substances 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 7
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
• 125000004423 acyloxy group Chemical group 0.000 claims description 6
• 239000000460 chlorine Substances 0.000 claims description 6
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
• 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 6
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
• 125000004149 thio group Chemical group *S* 0.000 claims description 6
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 6
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 5
• 125000003342 alkenyl group Chemical group 0.000 claims description 5
• 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 5
• 125000000464 thioxo group Chemical group S=* 0.000 claims description 5
• 125000000304 alkynyl group Chemical group 0.000 claims description 4
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims description 4
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 4
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• 125000002252 acyl group Chemical group 0.000 claims description 3
• 238000005917 acylation reaction Methods 0.000 claims description 3
• 150000001408 amides Chemical class 0.000 claims description 3
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 3
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
• 239000005977 Ethylene Substances 0.000 claims description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
• 230000010933 acylation Effects 0.000 claims description 2
• 230000003301 hydrolyzing effect Effects 0.000 claims description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
• 150000003246 quinazolines Chemical class 0.000 claims 14
• 230000001681 protective effect Effects 0.000 claims 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
• CMVNWVONJDMTSH-UHFFFAOYSA-N 7-bromo-2-methyl-1h-quinazolin-4-one Chemical compound C1=CC(Br)=CC2=NC(C)=NC(O)=C21 CMVNWVONJDMTSH-UHFFFAOYSA-N 0.000 claims 1
• 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims 1
• 239000008280 blood Substances 0.000 claims 1
• 230000001590 oxidative effect Effects 0.000 claims 1
• 239000000203 mixture Substances 0.000 description 309
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 213
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 131
• 239000000243 solution Substances 0.000 description 128
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 120
• 229910001868 water Inorganic materials 0.000 description 113
• 239000000047 product Substances 0.000 description 109
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 94
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 85
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 78
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 76
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 66
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 53
• 239000000741 silica gel Substances 0.000 description 53
• 229910002027 silica gel Inorganic materials 0.000 description 53
• 239000007858 starting material Substances 0.000 description 50
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
• 238000004587 chromatography analysis Methods 0.000 description 35
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 33
• 235000019341 magnesium sulphate Nutrition 0.000 description 33
• 239000007787 solid Substances 0.000 description 31
• 238000002844 melting Methods 0.000 description 30
• 230000008018 melting Effects 0.000 description 30
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 28
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
• 229940086542 triethylamine Drugs 0.000 description 26
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 23
• 238000012360 testing method Methods 0.000 description 23
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 22
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 21
• 150000001412 amines Chemical class 0.000 description 20
• 238000000921 elemental analysis Methods 0.000 description 20
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 18
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
• 239000012074 organic phase Substances 0.000 description 17
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 16
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
• 238000001819 mass spectrum Methods 0.000 description 15
• 239000002244 precipitate Substances 0.000 description 15
• 206010028980 Neoplasm Diseases 0.000 description 14
• 125000001309 chloro group Chemical group Cl* 0.000 description 13
• 239000003480 eluent Substances 0.000 description 13
• 150000002500 ions Chemical class 0.000 description 13
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• 239000012044 organic layer Substances 0.000 description 12
• 239000012267 brine Substances 0.000 description 11
• 239000000706 filtrate Substances 0.000 description 11
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
• 239000005711 Benzoic acid Substances 0.000 description 10
• 229910052731 fluorine Inorganic materials 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• 239000002904 solvent Substances 0.000 description 10
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 9
• 201000011510 cancer Diseases 0.000 description 9
• 238000010265 fast atom bombardment Methods 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 229910052708 sodium Inorganic materials 0.000 description 9
• 125000000335 thiazolyl group Chemical group 0.000 description 9
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 8
• XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 8
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• 229960000583 acetic acid Drugs 0.000 description 8
• 239000007864 aqueous solution Substances 0.000 description 8
• 238000003556 assay Methods 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 8
• 239000012071 phase Substances 0.000 description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
• 239000012265 solid product Substances 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
• PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 7
• 235000010233 benzoic acid Nutrition 0.000 description 7
• 238000004949 mass spectrometry Methods 0.000 description 7
• 230000002441 reversible effect Effects 0.000 description 7
• 239000012047 saturated solution Substances 0.000 description 7
• 125000001544 thienyl group Chemical group 0.000 description 7
• 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 7
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 6
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 6
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
• 239000004471 Glycine Substances 0.000 description 6
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
• 229910052794 bromium Inorganic materials 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 239000006260 foam Substances 0.000 description 6
• 238000002347 injection Methods 0.000 description 6
• 239000007924 injection Substances 0.000 description 6
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 6
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 125000004076 pyridyl group Chemical group 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
• 229910052717 sulfur Chemical group 0.000 description 6
• 239000011593 sulfur Chemical group 0.000 description 6
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
• QMNUDYFKZYBWQX-UHFFFAOYSA-N 3H-quinazolinyl-4-one Natural products C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 5
• ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 5
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 5
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
• 229910021529 ammonia Inorganic materials 0.000 description 5
• 150000001540 azides Chemical class 0.000 description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
• GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 5
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 5
• DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 5
• 125000006125 ethylsulfonyl group Chemical group 0.000 description 5
• 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 5
• 238000001704 evaporation Methods 0.000 description 5
• 230000008020 evaporation Effects 0.000 description 5
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 5
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 5
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