HU221622B1 - Kinazolinszármazékok, az ezeket tartalmazó gyógyászati készítmények és eljárás előállításukra - Google Patents

Info

Publication number

HU221622B1

HU221622B1 HU9300094A HU9300094A HU221622B1 HU 221622 B1 HU221622 B1 HU 221622B1 HU 9300094 A HU9300094 A HU 9300094A HU 9300094 A HU9300094 A HU 9300094A HU 221622 B1 HU221622 B1 HU 221622B1

Authority

HU

Hungary

Prior art keywords

amino

alkyl

alkoxy

formula

quinazoline

Prior art date

1992-01-20

Links

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• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
• 238000000034 method Methods 0.000 title claims description 26
• 230000008569 process Effects 0.000 title claims description 9
• 239000004480 active ingredient Substances 0.000 title abstract description 18
• 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract description 4
• -1 amino, carboxyl Chemical group 0.000 claims abstract description 298
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 130
• 150000001875 compounds Chemical class 0.000 claims abstract description 129
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 80
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 68
• 150000003839 salts Chemical class 0.000 claims abstract description 51
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 48
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 32
• 238000002360 preparation method Methods 0.000 claims abstract description 31
• 239000001257 hydrogen Substances 0.000 claims abstract description 26
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 23
• 125000001589 carboacyl group Chemical group 0.000 claims abstract description 16
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 15
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 15
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 13
• 150000002367 halogens Chemical class 0.000 claims abstract description 13
• 150000002431 hydrogen Chemical class 0.000 claims abstract description 13
• 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 9
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims abstract description 7
• 125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 5
• 150000003246 quinazolines Chemical class 0.000 claims description 50
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 40
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 34
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 33
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 18
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 17
• 125000003277 amino group Chemical group 0.000 claims description 16
• 229910052757 nitrogen Inorganic materials 0.000 claims description 16
• 125000003282 alkyl amino group Chemical group 0.000 claims description 15
• 239000002253 acid Substances 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 125000001424 substituent group Chemical group 0.000 claims description 12
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 230000002829 reductive effect Effects 0.000 claims description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 9
• MJKCGAHOCZLYDG-UHFFFAOYSA-N 6,7-dimethoxy-n-phenylquinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC=C1 MJKCGAHOCZLYDG-UHFFFAOYSA-N 0.000 claims description 8
• JFDWMFYUKLPRSP-UHFFFAOYSA-N 6-methyl-n-phenylquinazolin-4-amine Chemical compound C12=CC(C)=CC=C2N=CN=C1NC1=CC=CC=C1 JFDWMFYUKLPRSP-UHFFFAOYSA-N 0.000 claims description 8
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
• 125000006016 2-bromoethoxy group Chemical group 0.000 claims description 7
• GBJXFMREUNFKRX-UHFFFAOYSA-N 4-n-(4-aminophenyl)quinazoline-4,6-diamine Chemical compound C1=CC(N)=CC=C1NC1=NC=NC2=CC=C(N)C=C12 GBJXFMREUNFKRX-UHFFFAOYSA-N 0.000 claims description 7
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
• 125000005997 bromomethyl group Chemical group 0.000 claims description 7
• 239000000460 chlorine Substances 0.000 claims description 7
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 7
• CRZPVSMPJCPEPP-UHFFFAOYSA-N 4-([1,3]dioxolo[4,5-g]quinazolin-8-ylamino)phenol Chemical compound C1=CC(O)=CC=C1NC(C1=C2)=NC=NC1=CC1=C2OCO1 CRZPVSMPJCPEPP-UHFFFAOYSA-N 0.000 claims description 6
• VKOGLNSKGDTRGH-UHFFFAOYSA-N 4-[(6-methoxyquinazolin-4-yl)amino]phenol Chemical compound C12=CC(OC)=CC=C2N=CN=C1NC1=CC=C(O)C=C1 VKOGLNSKGDTRGH-UHFFFAOYSA-N 0.000 claims description 6
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 6
• BYBQXGBBLHNCIR-UHFFFAOYSA-N 4-(4-chloroanilino)quinazolin-8-ol Chemical compound N1=CN=C2C(O)=CC=CC2=C1NC1=CC=C(Cl)C=C1 BYBQXGBBLHNCIR-UHFFFAOYSA-N 0.000 claims description 5
• 125000004414 alkyl thio group Chemical group 0.000 claims description 5
• 150000001412 amines Chemical class 0.000 claims description 5
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
• ZFSSJGZFLIOOKN-UHFFFAOYSA-N 4-(4-methoxyanilino)quinazolin-8-ol Chemical compound C1=CC(OC)=CC=C1NC1=NC=NC2=C(O)C=CC=C12 ZFSSJGZFLIOOKN-UHFFFAOYSA-N 0.000 claims description 4
• YPBYGBLLRMWZAF-UHFFFAOYSA-N 4-[(6,7,8-trimethoxyquinazolin-4-yl)amino]phenol Chemical compound N1=CN=C2C(OC)=C(OC)C(OC)=CC2=C1NC1=CC=C(O)C=C1 YPBYGBLLRMWZAF-UHFFFAOYSA-N 0.000 claims description 4
• URJYCHBAPFKHRE-UHFFFAOYSA-N 8-methoxy-n-(4-methoxyphenyl)quinazolin-4-amine Chemical compound C1=CC(OC)=CC=C1NC1=NC=NC2=C(OC)C=CC=C12 URJYCHBAPFKHRE-UHFFFAOYSA-N 0.000 claims description 4
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 4
• 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims description 4
• MPIHIJBPYYKLEA-UHFFFAOYSA-N n-(4-chlorophenyl)-8-methoxyquinazolin-4-amine Chemical compound N1=CN=C2C(OC)=CC=CC2=C1NC1=CC=C(Cl)C=C1 MPIHIJBPYYKLEA-UHFFFAOYSA-N 0.000 claims description 4
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
• BWENYVDMLAZGTP-UHFFFAOYSA-N 7-methoxy-4-n-(3-methylphenyl)quinazoline-4,6-diamine Chemical compound C=12C=C(N)C(OC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 BWENYVDMLAZGTP-UHFFFAOYSA-N 0.000 claims description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
• 125000004432 carbon atom Chemical group C* 0.000 claims description 3
• 229910052801 chlorine Inorganic materials 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 238000005516 engineering process Methods 0.000 claims description 3
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
• VQIWZLBIZSXBLT-UHFFFAOYSA-N n-[4-(3-methylanilino)quinazolin-6-yl]benzamide Chemical compound CC1=CC=CC(NC=2C3=CC(NC(=O)C=4C=CC=CC=4)=CC=C3N=CN=2)=C1 VQIWZLBIZSXBLT-UHFFFAOYSA-N 0.000 claims description 3
• 239000001301 oxygen Substances 0.000 claims description 3
• 229910052760 oxygen Inorganic materials 0.000 claims description 3
• 239000008024 pharmaceutical diluent Substances 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• UFQQKRSIOKGSIU-UHFFFAOYSA-N 6,7-bis(2-methoxyethoxy)-n-(3-methylphenyl)quinazolin-4-amine Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 UFQQKRSIOKGSIU-UHFFFAOYSA-N 0.000 claims description 2
• IUTOPYXTRUDZEZ-UHFFFAOYSA-N COC1=CC=C(C=C1)NC2=NC=C3C=CC=C(C3=N2)OC Chemical compound COC1=CC=C(C=C1)NC2=NC=C3C=CC=C(C3=N2)OC IUTOPYXTRUDZEZ-UHFFFAOYSA-N 0.000 claims description 2
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
• 125000004423 acyloxy group Chemical group 0.000 claims description 2
• 230000002152 alkylating effect Effects 0.000 claims description 2
• 125000004429 atom Chemical group 0.000 claims description 2
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
• 238000006193 diazotization reaction Methods 0.000 claims description 2
• 239000011737 fluorine Substances 0.000 claims description 2
• 229910052731 fluorine Inorganic materials 0.000 claims description 2
• 125000000623 heterocyclic group Chemical group 0.000 claims description 2
• 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 2
• NZHRGFLNIISRAV-UHFFFAOYSA-N n-(3,4-dichlorophenyl)-6,7-dimethoxyquinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(Cl)C(Cl)=C1 NZHRGFLNIISRAV-UHFFFAOYSA-N 0.000 claims description 2
• JDEKFVYZUIPHET-UHFFFAOYSA-N n-(3-chlorophenyl)-6-methoxyquinazolin-4-amine Chemical compound C12=CC(OC)=CC=C2N=CN=C1NC1=CC=CC(Cl)=C1 JDEKFVYZUIPHET-UHFFFAOYSA-N 0.000 claims description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
• 238000005932 reductive alkylation reaction Methods 0.000 claims description 2
• 150000003573 thiols Chemical class 0.000 claims description 2
• 206010029897 Obsessive thoughts Diseases 0.000 claims 9
• 150000007513 acids Chemical class 0.000 claims 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 1
• 125000002252 acyl group Chemical group 0.000 claims 1
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 1
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
• VOPNWXZDJKCCRE-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 VOPNWXZDJKCCRE-UHFFFAOYSA-N 0.000 claims 1
• 229920001282 polysaccharide Polymers 0.000 claims 1
• 239000005017 polysaccharide Substances 0.000 claims 1
• 230000001093 anti-cancer Effects 0.000 abstract description 7
• 125000000547 substituted alkyl group Chemical group 0.000 abstract description 2
• 125000004122 cyclic group Chemical group 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 207
• 239000000203 mixture Substances 0.000 description 206
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 152
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 117
• 238000004458 analytical method Methods 0.000 description 102
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 77
• 239000011541 reaction mixture Substances 0.000 description 72
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 64
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 58
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
• 238000004440 column chromatography Methods 0.000 description 55
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
• 239000000243 solution Substances 0.000 description 49
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
• 239000000047 product Substances 0.000 description 39
• 239000007858 starting material Substances 0.000 description 36
• 238000005481 NMR spectroscopy Methods 0.000 description 34
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 29
• 235000019341 magnesium sulphate Nutrition 0.000 description 29
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 25
• 238000006243 chemical reaction Methods 0.000 description 25
• 239000002244 precipitate Substances 0.000 description 25
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 description 22
• 239000012044 organic layer Substances 0.000 description 22
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
• 239000003480 eluent Substances 0.000 description 21
• 210000004027 cell Anatomy 0.000 description 20
• 238000003756 stirring Methods 0.000 description 19
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 18
• 238000010992 reflux Methods 0.000 description 17
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
• 239000007787 solid Substances 0.000 description 16
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 15
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 15
• 238000010828 elution Methods 0.000 description 14
• 238000012360 testing method Methods 0.000 description 14
• NFBCSWGEYDCCDW-UHFFFAOYSA-N 4-n-(3-methylphenyl)quinazoline-4,6-diamine Chemical compound CC1=CC=CC(NC=2C3=CC(N)=CC=C3N=CN=2)=C1 NFBCSWGEYDCCDW-UHFFFAOYSA-N 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
• 206010028980 Neoplasm Diseases 0.000 description 13
• 238000003556 assay Methods 0.000 description 13
• 239000002585 base Substances 0.000 description 13
• 238000002844 melting Methods 0.000 description 13
• 230000008018 melting Effects 0.000 description 13
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
• 239000000463 material Substances 0.000 description 11
• 229910000027 potassium carbonate Inorganic materials 0.000 description 11
• 238000011282 treatment Methods 0.000 description 11
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
• 239000012071 phase Substances 0.000 description 9
• LLLHRNQLGUOJHP-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinazoline Chemical compound C1=NC(Cl)=C2C=C(OC)C(OC)=CC2=N1 LLLHRNQLGUOJHP-UHFFFAOYSA-N 0.000 description 8
• KPHNOFBKQHPSGB-UHFFFAOYSA-N 6-methoxy-4-(3-methylanilino)quinazolin-7-ol Chemical compound N1=CN=C2C=C(O)C(OC)=CC2=C1NC1=CC=CC(C)=C1 KPHNOFBKQHPSGB-UHFFFAOYSA-N 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
• 230000005764 inhibitory process Effects 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
• 230000002441 reversible effect Effects 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
• BUYIXGTWVMBDLP-UHFFFAOYSA-N 7-chloro-n-(3-methylphenyl)-6-nitroquinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC(=C(Cl)C=C3N=CN=2)[N+]([O-])=O)=C1 BUYIXGTWVMBDLP-UHFFFAOYSA-N 0.000 description 7
• 241001465754 Metazoa Species 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
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