NO331281B1 - Benzofuranderivat, farmasoytisk preparat og anvendelse av benzofuranderivat for fremstilling av medikament for behandling av pasienter som lider av trombose. - Google Patents

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Publication number

NO331281B1

NO331281B1 NO20044644A NO20044644A NO331281B1 NO 331281 B1 NO331281 B1 NO 331281B1 NO 20044644 A NO20044644 A NO 20044644A NO 20044644 A NO20044644 A NO 20044644A NO 331281 B1 NO331281 B1 NO 331281B1

Authority

NO

Norway

Prior art keywords

group

substituted

alkyl

alkoxy

alkyl group

Prior art date

2002-03-28

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• 239000003814 drug Substances 0.000 title claims abstract description 12
• 150000001907 coumarones Chemical class 0.000 title claims abstract description 10
• 208000007536 Thrombosis Diseases 0.000 title claims description 9
• 238000011282 treatment Methods 0.000 title claims description 7
• 238000004519 manufacturing process Methods 0.000 title claims description 5
• 239000000825 pharmaceutical preparation Substances 0.000 title claims description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 34
• 150000003839 salts Chemical class 0.000 claims abstract description 31
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 28
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 19
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 6
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 460
• 150000001875 compounds Chemical class 0.000 claims description 322
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 209
• -1 1,3-dioxanyl group Chemical group 0.000 claims description 205
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 155
• 125000002252 acyl group Chemical group 0.000 claims description 136
• 125000003277 amino group Chemical group 0.000 claims description 116
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 93
• 125000005936 piperidyl group Chemical group 0.000 claims description 88
• 125000003545 alkoxy group Chemical group 0.000 claims description 82
• 229920006395 saturated elastomer Polymers 0.000 claims description 59
• 125000002757 morpholinyl group Chemical group 0.000 claims description 53
• 125000004076 pyridyl group Chemical group 0.000 claims description 51
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 49
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 48
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 47
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 40
• 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 39
• 125000003118 aryl group Chemical group 0.000 claims description 31
• 125000004043 oxo group Chemical group O=* 0.000 claims description 30
• 125000000217 alkyl group Chemical group 0.000 claims description 27
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 24
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 22
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 19
• 125000004432 carbon atom Chemical group C* 0.000 claims description 17
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
• 125000001624 naphthyl group Chemical group 0.000 claims description 15
• 125000004193 piperazinyl group Chemical group 0.000 claims description 15
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 13
• 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 12
• 125000000335 thiazolyl group Chemical group 0.000 claims description 12
• 125000005843 halogen group Chemical group 0.000 claims description 11
• 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 claims description 10
• 229910052757 nitrogen Inorganic materials 0.000 claims description 10
• IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 claims description 9
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 9
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
• 125000000160 oxazolidinyl group Chemical group 0.000 claims description 9
• 125000004423 acyloxy group Chemical group 0.000 claims description 8
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• 125000004434 sulfur atom Chemical group 0.000 claims description 8
• 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 7
• LLLIOVFURPQSDG-KOMQPUFPSA-N C1C[C@@H](N(C)C)CC[C@@H]1C(=O)NC1=C(C(=O)NC=2N=CC(Cl)=CC=2)OC2=CC=CC=C12 Chemical compound C1C[C@@H](N(C)C)CC[C@@H]1C(=O)NC1=C(C(=O)NC=2N=CC(Cl)=CC=2)OC2=CC=CC=C12 LLLIOVFURPQSDG-KOMQPUFPSA-N 0.000 claims description 4
• AYULDSWFEDSWGB-RZDIXWSQSA-N CN(C)C(=O)c1ccc2oc(C(=O)Nc3ccc(Cl)cn3)c(NC(=O)[C@H]3CC[C@@H](CC3)N(C)C=O)c2c1 Chemical compound CN(C)C(=O)c1ccc2oc(C(=O)Nc3ccc(Cl)cn3)c(NC(=O)[C@H]3CC[C@@H](CC3)N(C)C=O)c2c1 AYULDSWFEDSWGB-RZDIXWSQSA-N 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• UOTKQHPUMBOXQW-XGAFWQRZSA-N Clc1ccc(NC(=O)c2oc3ccc(cc3c2NC(=O)[C@H]2CC[C@@H](CC2)N2CCCC2=O)C(=O)N2CCOCC2)nc1 Chemical compound Clc1ccc(NC(=O)c2oc3ccc(cc3c2NC(=O)[C@H]2CC[C@@H](CC2)N2CCCC2=O)C(=O)N2CCOCC2)nc1 UOTKQHPUMBOXQW-XGAFWQRZSA-N 0.000 claims description 3
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
• CELYUVVPMSYVOW-UAPYVXQJSA-N CN([C@H]1CC[C@@H](CC1)C(=O)Nc1c(oc2ccc(CCO)cc12)C(=O)Nc1ccc(Cl)cn1)C(C)=O Chemical compound CN([C@H]1CC[C@@H](CC1)C(=O)Nc1c(oc2ccc(CCO)cc12)C(=O)Nc1ccc(Cl)cn1)C(C)=O CELYUVVPMSYVOW-UAPYVXQJSA-N 0.000 claims description 2
• 239000004480 active ingredient Substances 0.000 claims description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 36
• 108010074860 Factor Xa Proteins 0.000 abstract description 13
• 239000003112 inhibitor Substances 0.000 abstract description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 9
• 239000001257 hydrogen Substances 0.000 abstract description 7
• 229910052739 hydrogen Inorganic materials 0.000 abstract description 7
• 229910052736 halogen Inorganic materials 0.000 abstract description 2
• 150000002367 halogens Chemical class 0.000 abstract description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
• 150000002431 hydrogen Chemical class 0.000 abstract 1
• 229910052760 oxygen Inorganic materials 0.000 abstract 1
• 239000001301 oxygen Substances 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 318
• 238000006243 chemical reaction Methods 0.000 description 226
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 196
• 239000000203 mixture Substances 0.000 description 169
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 156
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 146
• 239000002904 solvent Substances 0.000 description 132
• 239000000243 solution Substances 0.000 description 130
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 126
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 121
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 120
• 230000002829 reductive effect Effects 0.000 description 115
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 96
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 96
• 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 95
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 92
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 87
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 87
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 77
• 238000001816 cooling Methods 0.000 description 71
• 239000007864 aqueous solution Substances 0.000 description 68
• 238000001914 filtration Methods 0.000 description 67
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 64
• 229910052938 sodium sulfate Inorganic materials 0.000 description 64
• 235000011152 sodium sulphate Nutrition 0.000 description 64
• 239000000741 silica gel Substances 0.000 description 60
• 229910002027 silica gel Inorganic materials 0.000 description 60
• 238000004440 column chromatography Methods 0.000 description 58
• 239000003480 eluent Substances 0.000 description 58
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 53
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 53
• 239000012044 organic layer Substances 0.000 description 51
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 51
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 48
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 46
• 235000017557 sodium bicarbonate Nutrition 0.000 description 46
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 43
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 42
• 239000002244 precipitate Substances 0.000 description 41
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 40
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 38
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 34
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 33
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 33
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 32
• FMUOBRZKMCHAGE-UHFFFAOYSA-N methyl 4-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethoxy]-3-cyanobenzoate Chemical compound N#CC1=CC(C(=O)OC)=CC=C1OCC(=O)NC1=CC=C(Cl)C=N1 FMUOBRZKMCHAGE-UHFFFAOYSA-N 0.000 description 32
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 31
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 30
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 30
• 238000000034 method Methods 0.000 description 30
• 239000007858 starting material Substances 0.000 description 27
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
• 239000000047 product Substances 0.000 description 25
• CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 24
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 24
• 239000011541 reaction mixture Substances 0.000 description 24
• 150000001408 amides Chemical class 0.000 description 23
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 22
• BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 21
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 21
• 239000005457 ice water Substances 0.000 description 21
• 229910000027 potassium carbonate Inorganic materials 0.000 description 21
• 235000011181 potassium carbonates Nutrition 0.000 description 21
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
• 239000002585 base Substances 0.000 description 18
• 238000009835 boiling Methods 0.000 description 18
• 239000012046 mixed solvent Substances 0.000 description 18
• 239000002253 acid Substances 0.000 description 17
• 150000007530 organic bases Chemical class 0.000 description 17
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
• 150000002170 ethers Chemical class 0.000 description 16
• 239000012442 inert solvent Substances 0.000 description 16
• 238000010992 reflux Methods 0.000 description 16
• 229910000029 sodium carbonate Inorganic materials 0.000 description 16
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 15
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 150000007529 inorganic bases Chemical class 0.000 description 15
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
• 239000008096 xylene Substances 0.000 description 15
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 14
• 229910052783 alkali metal Inorganic materials 0.000 description 14
• GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 14
• MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 14
• 238000010438 heat treatment Methods 0.000 description 14
• 229910052751 metal Inorganic materials 0.000 description 14
• 239000002184 metal Substances 0.000 description 14
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
• 150000002825 nitriles Chemical class 0.000 description 14
• 229910000288 alkali metal carbonate Inorganic materials 0.000 description 13
• 150000008041 alkali metal carbonates Chemical class 0.000 description 13
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 13
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 13
• 229910000024 caesium carbonate Inorganic materials 0.000 description 13
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
• 150000001555 benzenes Chemical group 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
• 239000002198 insoluble material Substances 0.000 description 12
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 11
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 11
• 150000001412 amines Chemical class 0.000 description 11
• 235000009518 sodium iodide Nutrition 0.000 description 11
• QHKJIJXBJCOABP-UHFFFAOYSA-N 1-benzofuran-2-carboxamide Chemical compound C1=CC=C2OC(C(=O)N)=CC2=C1 QHKJIJXBJCOABP-UHFFFAOYSA-N 0.000 description 10
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
• 235000011054 acetic acid Nutrition 0.000 description 10
• 150000001298 alcohols Chemical class 0.000 description 10
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 10
• 230000002401 inhibitory effect Effects 0.000 description 10
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 10
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 9
• ORTSXIXFVOZCBP-UHFFFAOYSA-N 3-amino-n-(5-chloropyridin-2-yl)-1-benzofuran-2-carboxamide Chemical compound O1C2=CC=CC=C2C(N)=C1C(=O)NC1=CC=C(Cl)C=N1 ORTSXIXFVOZCBP-UHFFFAOYSA-N 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 9
• SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 8
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 8
• 150000003973 alkyl amines Chemical class 0.000 description 8
• HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 8
• 239000003146 anticoagulant agent Substances 0.000 description 8
• 229940127219 anticoagulant drug Drugs 0.000 description 8
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
• 239000003638 chemical reducing agent Substances 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 8
• HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 8
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
• 150000007524 organic acids Chemical class 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 8
• 150000003512 tertiary amines Chemical class 0.000 description 8
• IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 8
• IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 8
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