NO329542B1 - 4-anilinokinazolinderivater, fremgangsmate for fremstilling av slike, farmasoytiske preparater innholdende slike, slike forbindelser for anvendelse som medikament samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom - Google Patents

Info

Publication number

NO329542B1

NO329542B1 NO20044325A NO20044325A NO329542B1 NO 329542 B1 NO329542 B1 NO 329542B1 NO 20044325 A NO20044325 A NO 20044325A NO 20044325 A NO20044325 A NO 20044325A NO 329542 B1 NO329542 B1 NO 329542B1

Authority

NO

Norway

Prior art keywords

chloro

fluoroanilino

methoxy

quinazoline

methoxyquinazoline

Prior art date

2002-03-28

Links

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• 150000001875 compounds Chemical class 0.000 title claims description 160
• 238000000034 method Methods 0.000 title claims description 111
• 238000002360 preparation method Methods 0.000 title claims description 45
• 239000003814 drug Substances 0.000 title claims description 15
• 239000000825 pharmaceutical preparation Substances 0.000 title claims description 6
• 238000011282 treatment Methods 0.000 title description 28
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 11
• 201000010099 disease Diseases 0.000 title description 5
• 229940079593 drug Drugs 0.000 title description 5
• MTSNDBYBIZSILH-UHFFFAOYSA-N n-phenylquinazolin-4-amine Chemical class N=1C=NC2=CC=CC=C2C=1NC1=CC=CC=C1 MTSNDBYBIZSILH-UHFFFAOYSA-N 0.000 title description 5
• 238000006243 chemical reaction Methods 0.000 claims description 59
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 58
• 230000008569 process Effects 0.000 claims description 54
• 150000003246 quinazolines Chemical class 0.000 claims description 52
• 150000003839 salts Chemical class 0.000 claims description 52
• -1 methylenedioxypyrrolidinyl Chemical group 0.000 claims description 47
• 125000000217 alkyl group Chemical group 0.000 claims description 43
• 125000006239 protecting group Chemical group 0.000 claims description 34
• 125000001424 substituent group Chemical group 0.000 claims description 25
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 24
• 125000000524 functional group Chemical group 0.000 claims description 22
• 238000007796 conventional method Methods 0.000 claims description 20
• 239000002253 acid Substances 0.000 claims description 19
• 125000003545 alkoxy group Chemical group 0.000 claims description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
• 238000003776 cleavage reaction Methods 0.000 claims description 14
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 14
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
• 239000000460 chlorine Substances 0.000 claims description 13
• 229910052801 chlorine Inorganic materials 0.000 claims description 13
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
• 230000001028 anti-proliverative effect Effects 0.000 claims description 12
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
• 229910052757 nitrogen Inorganic materials 0.000 claims description 12
• 125000003282 alkyl amino group Chemical group 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 11
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 11
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
• 125000001589 carboacyl group Chemical group 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 9
• 150000002367 halogens Chemical class 0.000 claims description 9
• 230000007017 scission Effects 0.000 claims description 9
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 8
• 239000001257 hydrogen Substances 0.000 claims description 8
• 229910052739 hydrogen Inorganic materials 0.000 claims description 8
• 241001465754 Metazoa Species 0.000 claims description 7
• MORFQDRARBOZSN-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-piperidin-3-yloxyquinazolin-4-amine Chemical compound C=12C=C(OC3CNCCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F MORFQDRARBOZSN-UHFFFAOYSA-N 0.000 claims description 7
• DFNJBNWBONZOQL-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-piperidin-4-yloxyquinazolin-4-amine Chemical compound C=12C=C(OC3CCNCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F DFNJBNWBONZOQL-UHFFFAOYSA-N 0.000 claims description 7
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 7
• 238000005859 coupling reaction Methods 0.000 claims description 6
• RHHAVUPVXRAMLR-ZDUSSCGKSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-[(3s)-1-methylsulfonylpiperidin-3-yl]oxyquinazolin-4-amine Chemical compound C=12C=C(O[C@@H]3CN(CCC3)S(C)(=O)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F RHHAVUPVXRAMLR-ZDUSSCGKSA-N 0.000 claims description 6
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 229910052731 fluorine Inorganic materials 0.000 claims description 5
• 239000011737 fluorine Substances 0.000 claims description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
• 238000012986 modification Methods 0.000 claims description 5
• 230000004048 modification Effects 0.000 claims description 5
• SSOOQSBWLHGSCL-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-(piperidin-4-ylmethoxy)quinazolin-4-amine Chemical compound C=12C=C(OCC3CCNCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F SSOOQSBWLHGSCL-UHFFFAOYSA-N 0.000 claims description 5
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
• PQNRFGOXGMDMSI-UHFFFAOYSA-N [2-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-oxoethyl] acetate Chemical compound C=12C=C(OC3CN(CCC3)C(=O)COC(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F PQNRFGOXGMDMSI-UHFFFAOYSA-N 0.000 claims description 4
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 4
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
• 125000004414 alkyl thio group Chemical group 0.000 claims description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• DABOZAKYWAXTGO-ZDUSSCGKSA-N 1-[(2s)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C=12C=C(OC[C@H]3N(CCC3)C(=O)CO)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F DABOZAKYWAXTGO-ZDUSSCGKSA-N 0.000 claims description 3
• QEBRMJTUPMNDKF-HNNXBMFYSA-N 1-[(3s)-3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C=12C=C(O[C@@H]3CN(CCC3)C(=O)CN(C)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F QEBRMJTUPMNDKF-HNNXBMFYSA-N 0.000 claims description 3
• SIKHQLKPCASMEL-UHFFFAOYSA-N 1-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-hydroxyethanone Chemical compound C=12C=C(OC3CN(CCC3)C(=O)CO)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F SIKHQLKPCASMEL-UHFFFAOYSA-N 0.000 claims description 3
• BGJVGJZKZPYAMV-UHFFFAOYSA-N 1-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound C=12C=C(OC3CN(CCC3)C(=O)CN3CCCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F BGJVGJZKZPYAMV-UHFFFAOYSA-N 0.000 claims description 3
• FPPIVLMSIGJKPX-UHFFFAOYSA-N 1-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]ethanone Chemical compound C=12C=C(OC3CN(CCC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F FPPIVLMSIGJKPX-UHFFFAOYSA-N 0.000 claims description 3
• APWGONAWSQJAFF-UHFFFAOYSA-N 1-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-morpholin-4-ylethanone Chemical compound C=12C=C(OC3CCN(CC3)C(=O)CN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F APWGONAWSQJAFF-UHFFFAOYSA-N 0.000 claims description 3
• FYUILKSGHOYVJD-UHFFFAOYSA-N 1-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound C=12C=C(OC3CCN(CC3)C(=O)CN3CCCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F FYUILKSGHOYVJD-UHFFFAOYSA-N 0.000 claims description 3
• XLKMNDIRQXLLRJ-UHFFFAOYSA-N 1-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]ethanone Chemical compound C=12C=C(OC3CCN(CC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F XLKMNDIRQXLLRJ-UHFFFAOYSA-N 0.000 claims description 3
• FEGFNGQBRZUWHV-UHFFFAOYSA-N 2-(4-acetylpiperazin-1-yl)-1-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]ethanone Chemical compound C=12C=C(OC3CN(CCC3)C(=O)CN3CCN(CC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F FEGFNGQBRZUWHV-UHFFFAOYSA-N 0.000 claims description 3
• DIBGTMXGHUALIU-UHFFFAOYSA-N 2-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]acetamide Chemical compound C=12C=C(OC3CCN(CC(N)=O)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F DIBGTMXGHUALIU-UHFFFAOYSA-N 0.000 claims description 3
• MCQMHAGBYHUBTA-UHFFFAOYSA-N 2-[4-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]piperidin-1-yl]acetamide Chemical compound C=12C=C(OCC3CCN(CC(N)=O)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F MCQMHAGBYHUBTA-UHFFFAOYSA-N 0.000 claims description 3
• IIPZVWOEYKWBAM-IWPPFLRJSA-N [(4r)-4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxy-1-methylpyrrolidin-2-yl]-morpholin-4-ylmethanone Chemical compound C=12C=C(O[C@H]3CN(C)C(C3)C(=O)N3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F IIPZVWOEYKWBAM-IWPPFLRJSA-N 0.000 claims description 3
• QTMFEEDRXUIFDA-MRNPHLECSA-N [3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-[(2s)-1-methylpyrrolidin-2-yl]methanone Chemical compound C=12C=C(OC3CN(CCC3)C(=O)[C@H]3N(CCC3)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F QTMFEEDRXUIFDA-MRNPHLECSA-N 0.000 claims description 3
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
• 230000029936 alkylation Effects 0.000 claims description 3
• 238000005804 alkylation reaction Methods 0.000 claims description 3
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
• 125000002757 morpholinyl group Chemical group 0.000 claims description 3
• PNWLNPVNZZWWEA-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-6-[1-[3-(dimethylamino)propylsulfonyl]piperidin-4-yl]oxy-7-methoxyquinazolin-4-amine Chemical compound C=12C=C(OC3CCN(CC3)S(=O)(=O)CCCN(C)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F PNWLNPVNZZWWEA-UHFFFAOYSA-N 0.000 claims description 3
• QBSXCQDYNHLCCN-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-(1-methylpyrrolidin-3-yl)oxyquinazolin-4-amine Chemical compound C=12C=C(OC3CN(C)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F QBSXCQDYNHLCCN-UHFFFAOYSA-N 0.000 claims description 3
• BDLUIKGKNQFJIO-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-(1-methylsulfonylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C=C(OC3CCN(CC3)S(C)(=O)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F BDLUIKGKNQFJIO-UHFFFAOYSA-N 0.000 claims description 3
• HIOMOLUQMPMYMG-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine Chemical compound C=12C=C(OCC3CCN(C)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F HIOMOLUQMPMYMG-UHFFFAOYSA-N 0.000 claims description 3
• MORFQDRARBOZSN-LBPRGKRZSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-[(3s)-piperidin-3-yl]oxyquinazolin-4-amine Chemical compound C=12C=C(O[C@@H]3CNCCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F MORFQDRARBOZSN-LBPRGKRZSA-N 0.000 claims description 3
• SBMNEPVEDPDQNB-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-[2-(1-methylpiperidin-4-yl)ethoxy]quinazolin-4-amine Chemical compound C=12C=C(OCCC3CCN(C)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F SBMNEPVEDPDQNB-UHFFFAOYSA-N 0.000 claims description 3
• WYMUMLSWCGOSNO-CYBMUJFWSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-[[(2r)-1-methylpyrrolidin-2-yl]methoxy]quinazolin-4-amine Chemical compound C=12C=C(OC[C@@H]3N(CCC3)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F WYMUMLSWCGOSNO-CYBMUJFWSA-N 0.000 claims description 3
• OYWPEXPOKASXIN-CYBMUJFWSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-[[(2r)-1-methylsulfonylpyrrolidin-2-yl]methoxy]quinazolin-4-amine Chemical compound C=12C=C(OC[C@@H]3N(CCC3)S(C)(=O)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F OYWPEXPOKASXIN-CYBMUJFWSA-N 0.000 claims description 3
• 125000004193 piperazinyl group Chemical group 0.000 claims description 3
• 125000003386 piperidinyl group Chemical group 0.000 claims description 3
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
• KBIXTCZEFRUUAZ-CQSZACIVSA-N 1-[(2r)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]ethanone Chemical compound C=12C=C(OC[C@@H]3N(CCC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F KBIXTCZEFRUUAZ-CQSZACIVSA-N 0.000 claims description 2
• ALLCTPWIIGFMFC-HNNXBMFYSA-N 1-[(2s)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C=12C=C(OC[C@H]3N(CCC3)C(=O)CN(C)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F ALLCTPWIIGFMFC-HNNXBMFYSA-N 0.000 claims description 2
• GODGDPVZOQBJJT-AWEZNQCLSA-N 1-[(2s)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]-2-(methylamino)ethanone Chemical compound CNCC(=O)N1CCC[C@H]1COC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(Cl)=C1F GODGDPVZOQBJJT-AWEZNQCLSA-N 0.000 claims description 2
• FKIGKBRONDNFSA-UHFFFAOYSA-N 2-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]acetonitrile Chemical compound C=12C=C(OC3CCN(CC#N)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F FKIGKBRONDNFSA-UHFFFAOYSA-N 0.000 claims description 2
• OTPVAYXUVFDRBW-UHFFFAOYSA-N 2-[4-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]piperidin-1-yl]acetonitrile Chemical compound C=12C=C(OCC3CCN(CC#N)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F OTPVAYXUVFDRBW-UHFFFAOYSA-N 0.000 claims description 2
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• JOANRURMBNMJHR-UHFFFAOYSA-N 4-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]piperidine-1-carbonitrile Chemical compound C=12C=C(OCC3CCN(CC3)C#N)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F JOANRURMBNMJHR-UHFFFAOYSA-N 0.000 claims description 2
• 230000008878 coupling Effects 0.000 claims description 2
• 238000010168 coupling process Methods 0.000 claims description 2
• 229910052740 iodine Inorganic materials 0.000 claims description 2
• 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 2
• PUGRPTFZBHHZPM-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C=C(OC3CCN(C)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F PUGRPTFZBHHZPM-UHFFFAOYSA-N 0.000 claims description 2
• JPNAFMLRYCEEAB-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-[(1-methylpyrrolidin-3-yl)methoxy]quinazolin-4-amine Chemical compound C=12C=C(OCC3CN(C)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F JPNAFMLRYCEEAB-UHFFFAOYSA-N 0.000 claims description 2
• QBSXCQDYNHLCCN-GFCCVEGCSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-[(3r)-1-methylpyrrolidin-3-yl]oxyquinazolin-4-amine Chemical compound C=12C=C(O[C@H]3CN(C)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F QBSXCQDYNHLCCN-GFCCVEGCSA-N 0.000 claims description 2
• VAGCDXKHNHUMSZ-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-[1-(2-methoxyethyl)piperidin-4-yl]oxyquinazolin-4-amine Chemical compound C1CN(CCOC)CCC1OC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(Cl)=C1F VAGCDXKHNHUMSZ-UHFFFAOYSA-N 0.000 claims description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 2
• 150000003335 secondary amines Chemical class 0.000 claims description 2
• CHRMMMLUWHPZAH-UHFFFAOYSA-N 7-methoxyquinazoline Chemical compound C1=NC=NC2=CC(OC)=CC=C21 CHRMMMLUWHPZAH-UHFFFAOYSA-N 0.000 claims 2
• NOYQEMLFKXUGNZ-UHFFFAOYSA-N 1-[3-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]ethanone Chemical compound C=12C=C(OCC3CN(CC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F NOYQEMLFKXUGNZ-UHFFFAOYSA-N 0.000 claims 1
• 241000208202 Linaceae Species 0.000 claims 1
• 235000004431 Linum usitatissimum Nutrition 0.000 claims 1
• ITACCIZAPGMSPO-UHFFFAOYSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-[[1-(2-methoxyethyl)piperidin-4-yl]methoxy]quinazolin-4-amine Chemical compound C1CN(CCOC)CCC1COC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(Cl)=C1F ITACCIZAPGMSPO-UHFFFAOYSA-N 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 476
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 237
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 134
• 239000000047 product Substances 0.000 description 133
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 119
• 239000000203 mixture Substances 0.000 description 113
• 238000001819 mass spectrum Methods 0.000 description 107
• 239000000243 solution Substances 0.000 description 103
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