SI9600102A - Quinazoline derivatives - Google Patents

Info

Publication number

SI9600102A

SI9600102A SI9600102A SI9600102A SI9600102A SI 9600102 A SI9600102 A SI 9600102A SI 9600102 A SI9600102 A SI 9600102A SI 9600102 A SI9600102 A SI 9600102A SI 9600102 A SI9600102 A SI 9600102A

Authority

SI

Slovenia

Prior art keywords

amine

quinazolin

phenyl

ethynyl

alkyl

Prior art date

1995-03-30

Links

• Espacenet
• Global Dossier
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• 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title 1
• -1 4-(substitutedphenylamino)quinazoline Chemical class 0.000 claims abstract description 217
• 150000001875 compounds Chemical class 0.000 claims abstract description 111
• 150000003839 salts Chemical class 0.000 claims abstract description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
• 201000010099 disease Diseases 0.000 claims abstract description 9
• 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 53
• 125000000217 alkyl group Chemical group 0.000 claims description 39
• 238000000034 method Methods 0.000 claims description 37
• 229910052739 hydrogen Inorganic materials 0.000 claims description 34
• 239000001257 hydrogen Substances 0.000 claims description 34
• 229910052757 nitrogen Inorganic materials 0.000 claims description 31
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
• 150000001412 amines Chemical class 0.000 claims description 28
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 25
• 150000002431 hydrogen Chemical class 0.000 claims description 22
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 21
• 229910052760 oxygen Inorganic materials 0.000 claims description 18
• 229910052717 sulfur Inorganic materials 0.000 claims description 18
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
• 238000002360 preparation method Methods 0.000 claims description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
• 125000003282 alkyl amino group Chemical group 0.000 claims description 14
• 239000001301 oxygen Substances 0.000 claims description 14
• 239000011593 sulfur Substances 0.000 claims description 14
• 125000005842 heteroatom Chemical group 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 125000004432 carbon atom Chemical group C* 0.000 claims description 12
• 125000004122 cyclic group Chemical group 0.000 claims description 12
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• 229910052799 carbon Inorganic materials 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 9
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
• 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 150000002367 halogens Chemical class 0.000 claims description 8
• 125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 claims description 8
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 7
• 229920000642 polymer Polymers 0.000 claims description 7
• 230000008569 process Effects 0.000 claims description 7
• 241000124008 Mammalia Species 0.000 claims description 6
• 125000004423 acyloxy group Chemical group 0.000 claims description 6
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 150000001721 carbon Chemical group 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
• MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical group C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims description 4
• MTLKTHNRZJKPRP-UHFFFAOYSA-N 2-[4-(3-ethynylanilino)-6-(2-methoxyethoxy)quinazolin-7-yl]oxyethanol Chemical compound N1=CN=C2C=C(OCCO)C(OCCOC)=CC2=C1NC1=CC=CC(C#C)=C1 MTLKTHNRZJKPRP-UHFFFAOYSA-N 0.000 claims description 4
• XSMVZQAPXNUGBP-UHFFFAOYSA-N 2-[4-(3-ethynylanilino)-7-(2-methoxyethoxy)quinazolin-6-yl]oxyethyl acetate Chemical compound C=12C=C(OCCOC(C)=O)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 XSMVZQAPXNUGBP-UHFFFAOYSA-N 0.000 claims description 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• TZHTWWZUWBDHPB-UHFFFAOYSA-N 2-[4-(3-ethynylanilino)-6-(2-methoxyethoxy)quinazolin-7-yl]oxyethyl acetate Chemical compound N1=CN=C2C=C(OCCOC(C)=O)C(OCCOC)=CC2=C1NC1=CC=CC(C#C)=C1 TZHTWWZUWBDHPB-UHFFFAOYSA-N 0.000 claims description 3
• YWSAEKIQJPQSDJ-UHFFFAOYSA-N 2-[4-(3-ethynylanilino)-7-(2-hydroxyethoxy)quinazolin-6-yl]oxyethanol Chemical compound C=12C=C(OCCO)C(OCCO)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 YWSAEKIQJPQSDJ-UHFFFAOYSA-N 0.000 claims description 3
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• NRKMCAKKJSZIRN-UHFFFAOYSA-N 4-n-(3-ethynylphenyl)quinazoline-4,6-diamine Chemical compound C12=CC(N)=CC=C2N=CN=C1NC1=CC=CC(C#C)=C1 NRKMCAKKJSZIRN-UHFFFAOYSA-N 0.000 claims description 3
• MLFVZJQGCZIVJI-UHFFFAOYSA-N 4-n-(3-ethynylphenyl)quinazoline-4,7-diamine Chemical compound N=1C=NC2=CC(N)=CC=C2C=1NC1=CC=CC(C#C)=C1 MLFVZJQGCZIVJI-UHFFFAOYSA-N 0.000 claims description 3
• AZMJCKIZWVLDEH-UHFFFAOYSA-N 6,7-diethoxy-n-(3-ethynylphenyl)-2h-quinazolin-1-amine Chemical compound C1=2C=C(OCC)C(OCC)=CC=2C=NCN1NC1=CC=CC(C#C)=C1 AZMJCKIZWVLDEH-UHFFFAOYSA-N 0.000 claims description 3
• 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 3
• XOTGKYTUNDYTBS-UHFFFAOYSA-N N-(3-ethynylphenyl)-6,7-dimethoxy-4-quinazolinamine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 XOTGKYTUNDYTBS-UHFFFAOYSA-N 0.000 claims description 3
• 150000001345 alkine derivatives Chemical class 0.000 claims description 3
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• 229940079593 drug Drugs 0.000 claims description 3
• OVBFNQKSLJYVCB-UHFFFAOYSA-N n-(4-ethynylphenyl)-6,7-dimethoxyquinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(C#C)C=C1 OVBFNQKSLJYVCB-UHFFFAOYSA-N 0.000 claims description 3
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
• 125000005544 phthalimido group Chemical group 0.000 claims description 3
• 229910052727 yttrium Inorganic materials 0.000 claims description 3
• 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 2
• KOQIAZNBAWFSQM-UHFFFAOYSA-N 2-[4-(3-ethynylanilino)-7-(2-methoxyethoxy)quinazolin-6-yl]oxyethanol Chemical compound C=12C=C(OCCO)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 KOQIAZNBAWFSQM-UHFFFAOYSA-N 0.000 claims description 2
• RPBDPTCBOMUIEM-UHFFFAOYSA-N 2-[4-(3-ethynylanilino)quinazolin-6-yl]guanidine Chemical compound C12=CC(NC(=N)N)=CC=C2N=CN=C1NC1=CC=CC(C#C)=C1 RPBDPTCBOMUIEM-UHFFFAOYSA-N 0.000 claims description 2
• OPZQXOBOVGSGMM-UHFFFAOYSA-N 6,7-bis(2-chloroethoxy)-n-(3-ethynylphenyl)quinazolin-4-amine Chemical compound C=12C=C(OCCCl)C(OCCCl)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 OPZQXOBOVGSGMM-UHFFFAOYSA-N 0.000 claims description 2
• KNIMCHSAQRHRKH-UHFFFAOYSA-N 6,7-dibutoxy-n-(3-ethynylphenyl)-2h-quinazolin-1-amine Chemical compound C1=2C=C(OCCCC)C(OCCCC)=CC=2C=NCN1NC1=CC=CC(C#C)=C1 KNIMCHSAQRHRKH-UHFFFAOYSA-N 0.000 claims description 2
• DBLVDARHJKFUSK-UHFFFAOYSA-N 6-(2-chloroethoxy)-n-(3-ethynylphenyl)-7-(2-methoxyethoxy)quinazolin-4-amine Chemical compound C=12C=C(OCCCl)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 DBLVDARHJKFUSK-UHFFFAOYSA-N 0.000 claims description 2
• BIHHIONDWPZXJC-UHFFFAOYSA-N 7-(2-chloroethoxy)-n-(3-ethynylphenyl)-6-(2-methoxyethoxy)quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCCCl)C(OCCOC)=CC2=C1NC1=CC=CC(C#C)=C1 BIHHIONDWPZXJC-UHFFFAOYSA-N 0.000 claims description 2
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
• 229910021386 carbon form Inorganic materials 0.000 claims description 2
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 2
• MJGHBVDYEIMCDA-UHFFFAOYSA-N methyl 4-(3-ethynylanilino)quinazoline-6-carboxylate Chemical compound C12=CC(C(=O)OC)=CC=C2N=CN=C1NC1=CC=CC(C#C)=C1 MJGHBVDYEIMCDA-UHFFFAOYSA-N 0.000 claims description 2
• YVEQUSIQTPNUHB-UHFFFAOYSA-N n-(3-ethynyl-2-methylphenyl)-6,7-bis(2-methoxyethoxy)-2h-quinazolin-1-amine Chemical compound C1=2C=C(OCCOC)C(OCCOC)=CC=2C=NCN1NC1=CC=CC(C#C)=C1C YVEQUSIQTPNUHB-UHFFFAOYSA-N 0.000 claims description 2
• FFNSJZNWHNDAKT-UHFFFAOYSA-N n-(3-ethynyl-4-fluorophenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=C(F)C(C#C)=C1 FFNSJZNWHNDAKT-UHFFFAOYSA-N 0.000 claims description 2
• UEKLAZGZLXRYAO-UHFFFAOYSA-N n-(3-ethynyl-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(C#C)=C1 UEKLAZGZLXRYAO-UHFFFAOYSA-N 0.000 claims description 2
• FKTOOVAYMNBBOM-UHFFFAOYSA-N n-(3-ethynylphenyl)-6,7-di(propan-2-yloxy)-2h-quinazolin-1-amine Chemical compound C1=2C=C(OC(C)C)C(OC(C)C)=CC=2C=NCN1NC1=CC=CC(C#C)=C1 FKTOOVAYMNBBOM-UHFFFAOYSA-N 0.000 claims description 2
• XNMSCKOLUZHGET-UHFFFAOYSA-N n-(3-ethynylphenyl)-6-methylsulfonylquinazolin-4-amine Chemical compound C12=CC(S(=O)(=O)C)=CC=C2N=CN=C1NC1=CC=CC(C#C)=C1 XNMSCKOLUZHGET-UHFFFAOYSA-N 0.000 claims description 2
• AWQMPORAKHHXOC-UHFFFAOYSA-N n-(3-ethynylphenyl)-7-methoxyquinazolin-4-amine Chemical compound N=1C=NC2=CC(OC)=CC=C2C=1NC1=CC=CC(C#C)=C1 AWQMPORAKHHXOC-UHFFFAOYSA-N 0.000 claims description 2
• PXVOMAUMUFQFKF-UHFFFAOYSA-N n-(3-ethynylphenyl)-7-nitroquinazolin-4-amine Chemical compound N=1C=NC2=CC([N+](=O)[O-])=CC=C2C=1NC1=CC=CC(C#C)=C1 PXVOMAUMUFQFKF-UHFFFAOYSA-N 0.000 claims description 2
• LBAXXGJEHLZEQP-UHFFFAOYSA-N n-(3-ethynylphenyl)-[1,3]dioxolo[4,5-g]quinazolin-8-amine Chemical compound C#CC1=CC=CC(NC=2C3=CC=4OCOC=4C=C3N=CN=2)=C1 LBAXXGJEHLZEQP-UHFFFAOYSA-N 0.000 claims description 2
• MZSAGCRPYHVVDD-UHFFFAOYSA-N n-(5-ethynyl-2-methylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC(C#C)=CC=C1C MZSAGCRPYHVVDD-UHFFFAOYSA-N 0.000 claims description 2
• 239000002243 precursor Substances 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 26
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 7
• DUGLQQONGNNEMW-UHFFFAOYSA-N 2-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]acetamide Chemical compound C=12C=C(CC(N)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 DUGLQQONGNNEMW-UHFFFAOYSA-N 0.000 claims 2
• PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims 2
• 125000003118 aryl group Chemical group 0.000 claims 2
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims 1
• COYVNRXIBHVWOA-UHFFFAOYSA-N 2-[4-(3-ethynylanilino)-7-propan-2-yloxyquinazolin-6-yl]acetamide Chemical compound C=12C=C(CC(N)=O)C(OC(C)C)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 COYVNRXIBHVWOA-UHFFFAOYSA-N 0.000 claims 1
• TYRDQXAAPHCGHJ-UHFFFAOYSA-N 2-[4-(3-ethynylanilino)-7-propoxyquinazolin-6-yl]acetamide Chemical compound C=12C=C(CC(N)=O)C(OCCC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 TYRDQXAAPHCGHJ-UHFFFAOYSA-N 0.000 claims 1
• OLQYOMSHERWQMA-UHFFFAOYSA-N 2-[7-ethoxy-4-(3-ethynylanilino)quinazolin-6-yl]acetamide Chemical compound C=12C=C(CC(N)=O)C(OCC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 OLQYOMSHERWQMA-UHFFFAOYSA-N 0.000 claims 1
• NWUMMKLVEFBCRV-UHFFFAOYSA-N 2-[[1-(3-ethynyl-2-methylanilino)-7-(2-hydroxyethoxy)-2h-quinazolin-6-yl]oxy]ethanol Chemical compound C1=CC=C(C#C)C(C)=C1NN1C2=CC(OCCO)=C(OCCO)C=C2C=NC1 NWUMMKLVEFBCRV-UHFFFAOYSA-N 0.000 claims 1
• BLEIGNISAJGLGG-UHFFFAOYSA-N 2-[[1-(3-ethynylanilino)-7-(2-hydroxyethoxy)-2h-quinazolin-6-yl]oxy]ethanol Chemical compound C1=2C=C(OCCO)C(OCCO)=CC=2C=NCN1NC1=CC=CC(C#C)=C1 BLEIGNISAJGLGG-UHFFFAOYSA-N 0.000 claims 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims 1
• XCMVOGXJGDEPQM-UHFFFAOYSA-N 3-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]propanamide Chemical compound C=12C=C(CCC(N)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 XCMVOGXJGDEPQM-UHFFFAOYSA-N 0.000 claims 1
• HZDFRVLTROVMEI-UHFFFAOYSA-N 3-[4-(3-ethynylanilino)-7-propan-2-yloxyquinazolin-6-yl]propanamide Chemical compound C=12C=C(CCC(N)=O)C(OC(C)C)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 HZDFRVLTROVMEI-UHFFFAOYSA-N 0.000 claims 1
• OIESHIYYNQZRCL-UHFFFAOYSA-N 3-[4-(3-ethynylanilino)-7-propoxyquinazolin-6-yl]propanamide Chemical compound C=12C=C(CCC(N)=O)C(OCCC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 OIESHIYYNQZRCL-UHFFFAOYSA-N 0.000 claims 1
• JIKUZGKMYUACPU-UHFFFAOYSA-N 3-[7-ethoxy-4-(3-ethynylanilino)quinazolin-6-yl]propanamide Chemical compound C=12C=C(CCC(N)=O)C(OCC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 JIKUZGKMYUACPU-UHFFFAOYSA-N 0.000 claims 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
• SRGSZEVWWPMFLC-UHFFFAOYSA-N methyl 4-(3-ethynylanilino)quinazoline-7-carboxylate Chemical compound N=1C=NC2=CC(C(=O)OC)=CC=C2C=1NC1=CC=CC(C#C)=C1 SRGSZEVWWPMFLC-UHFFFAOYSA-N 0.000 claims 1
• RMTOBWAVMBQAOO-UHFFFAOYSA-N n-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-2h-quinazolin-1-amine Chemical compound C1=2C=C(OCCOC)C(OCCOC)=CC=2C=NCN1NC1=CC=CC(C#C)=C1 RMTOBWAVMBQAOO-UHFFFAOYSA-N 0.000 claims 1
• YHGQPRLZLURJKG-UHFFFAOYSA-N n-(3-ethynylphenyl)-6,7-dimethoxy-2h-quinazolin-1-amine Chemical compound C1=2C=C(OC)C(OC)=CC=2C=NCN1NC1=CC=CC(C#C)=C1 YHGQPRLZLURJKG-UHFFFAOYSA-N 0.000 claims 1
• 238000011282 treatment Methods 0.000 abstract description 12
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
• 239000000047 product Substances 0.000 description 129
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 100
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 73
• 239000007787 solid Substances 0.000 description 64
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
• 239000000203 mixture Substances 0.000 description 46
• 239000011541 reaction mixture Substances 0.000 description 42
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
• 238000004128 high performance liquid chromatography Methods 0.000 description 30
• 239000000243 solution Substances 0.000 description 30
• 239000002904 solvent Substances 0.000 description 30
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 29
• 206010028980 Neoplasm Diseases 0.000 description 27
• 239000012267 brine Substances 0.000 description 26
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-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
• 239000011734 sodium Substances 0.000 description 22
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 22
• 238000006243 chemical reaction Methods 0.000 description 21
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
• 239000002585 base Substances 0.000 description 20
• 125000005843 halogen group Chemical group 0.000 description 20
• 239000000741 silica gel Substances 0.000 description 19
• 229910002027 silica gel Inorganic materials 0.000 description 19
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 18
• NNKQLUVBPJEUOR-UHFFFAOYSA-N 3-ethynylaniline Chemical compound NC1=CC=CC(C#C)=C1 NNKQLUVBPJEUOR-UHFFFAOYSA-N 0.000 description 17
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